Condition: Metastatic Castration Resistant Prostate Cancer (mCRPC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03874884

Sponsor: Peter MacCallum Cancer Centre, Australia

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Patients must meet all of the following criteria for study entry: 1. Patient must be ≥ 18 years of age and must have provided written informed consent. 2. Histologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell differentiation. 3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 (see Appendix 1). 4. For dose escalation (dose levels 1-9) and expansion cohorts, patients must have had at least one prior line of taxane (docetaxel) chemotherapy either in the hormone sensitive or castrate resistant setting unless the patient is deemed medically unsuitable for chemotherapy. If a patient has had docetaxel chemotherapy twice, this will be considered one line. For the continuous olaparib dose cohort (DE #2) patients can have had docetaxel however this is not required for eligibility. 5. Patients must have progressed on a second generation AR targeted agent (e.g. enzalutamide, abiraterone, darolutamide and/or apalutamide). Determination of disease progression on second generation AR targeted agent will be made by the local investigator. 6. Patients must have progressive disease for study entry. This is defined by PCWG3 as any one of the following:
• PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement. The PSA value at screening should be ≥ 10ng/ml.
• Soft tissue or visceral disease progression as per RECIST 1.1 criteria (see Appendix 2)
• Bone progression: ≥ 2 new lesions on bone scan (Appendix 2) 7. At least 3 weeks since the completion of surgery or radiotherapy prior to registration. Any clinically relevant sequelae from the surgery or radiotherapy must have improved to grade 1 prior to registration. 8. Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist). Patients without prior surgical castration must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) therapy throughout the duration of study treatment. 9. Serum testosterone levels ≤ 50ng/dL (≤ 1.75nmol/L) within 28 days before registration. 10. Imaging evidence of metastatic disease documented with either bone scan or CT scan (Appendix 2). 11. Prior prostate cancer vaccine therapy, radiation therapy, systemic therapies, diethylstilboestrol (DES) or other estrogens, bicalutamide, flutamide or nilutamide are allowed up to 28 days prior to trial registration. Note: bicalutamide, flutamide or nilutamide must be discontinued within 4 weeks of registration. 12. Significant PSMA avidity on 68Ga/18F-PSMA PET/CT, defined as a minimum uptake of SUVmax 15 at a site of disease, and SUVmax > 10 at other sites of disease ≥10mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact). 13. Patients must have a life expectancy ≥ 24 weeks. 14. Patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception (see section 11.7.4 for acceptable methods). 15. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled assessments including completing Patient Reported Outcomes (PRO) instruments. 16. Patients must have adequate bone marrow, hepatic and renal function documented within 28 days prior to registration, defined as:
• Haemoglobin ≥ 100 g/L independent of transfusions (no red blood cell transfusion in last 8 weeks)
• Absolute neutrophil count ≥ 1.5x109/L
• Platelets ≥ 150 x109/L
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome where this applies for the unconjugated bilirubin.
• Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT) ≤ 2.5 x ULN if there is no evidence of liver metastasis or ≤ 5 x ULN in the presence of liver metastases.
• Albumin ≥ 30 g/L
• Adequate renal function: patients must have creatinine clearance estimated of ≥ 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test to appendix 5). 17. Patients who are deemed by PSMA imaging to have readily accessible disease will be required to consent to 3 serial tumour biopsies
• at screening, post combination treatment (at any time between weeks 2-4) and in the event of disease progression.

Exclusion Criteria:

• Patients must not meet any of the following criteria for study entry: 1. Site(s) of disease that are FDG positive with low PSMA expression defined by PSMA SUVmax < 10. 2. Extensive marrow disease defined by a "Super Scan" on bone scintigraphy or diffuse marrow infiltration on PSMA PET. 3. Previous history or presence of brain metastases or leptomeningeal metastases. A scan to confirm the absence of brain metastases is not required if there is no clinical history of this. 4. Surgery or radiotherapy within < 3 weeks of registration (except for palliative reasons). Patients must have recovered from any effects of any major surgery. 5. Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for ≥ 4 weeks. 6. Any prior exposure to 177Lu-PSMA, cabazitaxel, platinums, PARP inhibitors, mitoxantrone or cyclophosphamide. 7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent thromboembolic events (<6 months ago), uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or psychiatric illness/social situations that is likely to impede participation and /or compliance in the study. 8. Persistent toxicities [Common Terminology Criteria for Adverse Event (CTCAE) ≥ grade 2] caused by previous cancer therapy, excluding alopecia. 9. Other malignancies within the previous 2-years other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months. 10. Previous history of interstitial lung disease or non-infectious pneumonitis. 11. Patients with a history or clinical features suggestive of myelodysplastic syndrome / acute myeloid leukaemia. 12. Patients unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with the absorption of the study medication. 13. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation > 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome. 14. Known hypersensitivity to olaparib or any of the excipients of olaparib. 15. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV1/2). Only need to check this if there is a clinical history. HIV-infected (HIV1/2 antibody-positive) patients may participate if they meet all the following eligibility requirements:
• They must be on an anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on this same regimen; the most recent undetectable viral load must be within the past 12 weeks.
• They must have a CD4 count ≥ 250 cells/µL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/µl over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy-induced bone marrow suppression.
• For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/µl during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy.
• They must have an undetectable viral load and a CD4 count ≥ 250 cells/µL within 7 days of enrolment.
• They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months. 16. Patients with known active hepatitis (i.e. Hepatitis B or C). Only need to check this if there is a clinical history.
• Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 17. Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. 18. Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital and enzalutamide and 3 weeks for other agents. 19. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT). 20. Participation in another clinical study with an investigational product or another systemic therapy administered in the last 3 weeks.

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Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04188587

Sponsor: Nanjing First Hospital, Nanjing Medical University

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum 90 Years
• Gender: Male

Exclusion Criteria:

1. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed.
2. Hemoglobin<80g/L;Hemameba<2.5×109/L;Thrombocyte<70g/L
3. Glomerular filtration rate<50ml/min
4. Serum creatinine>130umol/L;Total bilirubin>2mg/L;Albumin<30g/L.
5. International normalized ratio（INR）>1,5
6. Alanine aminotransferase, aspartate aminotransferase is 5 times larger than normal value

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Condition: Metastatic Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04134208

Sponsor: M.D. Anderson Cancer Center

Phase: Phase 4

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Histologically or cytologically proven prostate carcinoma
• Documented evidence of M1 disease by American Joint Committee on Cancer (AJCC) staging by bone scan, CT and magnetic resonance imaging (MRI)
• Castration naive disease, no prior systemic therapy for prostate cancer
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Ability to understand and willingness to sign informed consent

Exclusion Criteria:

• Known brain metastasis
• Small cell carcinoma of the prostate

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Condition: Bone Metastases, Prostate Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02969564

Sponsor: Osman Ratib

Phase:

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Oligo- metastatic patient with prostate cancer and bone lesions (up to five metastases) based on scintigraphy and whole-body SPECT/CT (staging or recurrence).
• Patient must be able to provide informed consent.
• Patient is ≥ 18 years old

Exclusion Criteria:

• Patient with another active malignancy.
• Patient is < 18 years old
• Patients with contraindications of MRI procedure (metal implants, cardiac pacemakers, old type of prosthesis)
• Patients with severe renal impairment (MDRD < 30)

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Condition: Prostatic Neoplasms

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02364531

Sponsor: Janssen Inc.

Phase:

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Participants must have a confirmed diagnosis of metastatic castrate-resistant prostate cancer (mCRPC) according to medical history and have rising Prostate-Specific Antigen (PSA) levels or radiographic progression (documented by previous positive bone scan or metastatic lesions identified on CT or MRI) despite ongoing conventional Androgen deprivation therapy (ADT)
• Participant (or legally accepted representative) must be able to sign an informed consent form (ICF) indicating that they understand the procedures for data collection and are willing to participate in the study
• Participant must be able to understand and complete study questionnaires
• Abiraterone Acetate (ZYTIGA) has been chosen as the treatment for mCRPC disease progression as part of standard of care
• Male participants aged greater than (>) 18 years

Exclusion Criteria:

• Participants currently participating in another investigational clinical study of ZYTIGA or any other investigational drug
• Participants who have received prior cytotoxic chemotherapy for prostate cancer while receiving ADT
• Participants who have any other condition that, in the opinion of the investigator, may affect the participants health or outcome of the trial (i.e. uncontrolled disease)
• Life expectancy of less than (<) 1 year
• History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer

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Condition: Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Solid Tumor, Adult, Solid Tumor, Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04927663

Sponsor: Rahul Aggarwal

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. 1.

Disease Characteristics:

• by cohort, as defined by:
• COHORT A: Histologically confirmed metastatic solid tumor malignancy.
• COHORT B: Metastatic castration-resistant prostate cancer with progression on systemic therapies by PCWG3.
• COHORT C: Metastatic advanced solid tumor malignancy other than prostate adenocarcinoma with at least one metastasis on conventional imaging. 2. The subject is able and willing to comply with study procedures and provide signed and dated informed consent. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. Age 18 years or older at the time of study entry. 5. Adequate organ function, as defined by: 1. Serum creatinine =< 1.5 x upper limit of normal (ULN) OR estimated creatinine clearance > 50 ml/min 2. Total bilirubin =< 1.5 x ULN 3. Hemoglobin >= 8.0 g/dL 4. Platelet count >= 50,000/microliter 5. Absolute neutrophil count >= 1000/microliter

Exclusion Criteria:

1. Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
2. Concurrent treatment with any dose of systemic glucocorticoids within 7 days prior to cycle 1 day 1 (C1D1).
3. History of adrenal insufficiency requiring use of systemic glucocorticoid replacement.
4. History of Cushing's disease or Cushing's syndrome.
5. Any condition that, in the opinion of the principal investigator, would impair the patient's ability to comply with study procedures.
6. Contra-indication to MRI (e.g. pacemaker placement, severe claustrophobia) (applicable only for patients scheduled for PET/MRI).

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Condition: Prostate Cancer, Renal Cancer, Urethral Cancer, Advanced Solid Tumor, Metastatic Castration-resistant Prostate Cancer, Solid Tumor, Adult

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05888532

Sponsor: Rahul Aggarwal

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

1. 1.

Disease Characteristics:

• by cohort, as defined by: Cohort A:
• Histologically-confirmed metastatic solid tumor malignancy (3 Male, 3 Female)
• Locally advanced or metastatic disease on conventional imaging Cohort B:
• Histologically-confirmed metastatic renal cell carcinoma (any histologic sub-type) or urothelial carcinoma
• Locally advanced or metastatic disease on conventional imaging Cohort C:
• Histologically-confirmed prostate adenocarcinoma
• Metastatic castration resistant prostate cancer by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria 2. Planned treatment with immune checkpoint inhibitor (Cohorts B and C only) 3. Willing to undergo paired tumor biopsies and has safely accessible bone or soft tissue lesion (Cohorts B and C only) 4. The subject is able and willing to comply with study procedures and provide signed and dated informed consent. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 6. Age 18 years or older at the time of study entry. 7. Adequate organ function, as defined by:
• Serum creatinine <= 1.5 x upper limit of normal (ULN) or estimated creatinine clearance > 60 mL/min
• Total bilirubin <= 1.5 x ULN (< 3 x ULN in patients with documented or suspected Gilbert's).
• Hemoglobin >= 8.0 g/dL
• Platelet count >= 75,000/microliter
• Absolute neutrophil count ≥ 1000/microliter 8. Patients must not be pregnant or breast feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of PET Imaging scan. Effective contraception (men and women) must be used in subjects of child-bearing potential.

Exclusion Criteria:

1. Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
2. Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.
3. Is currently pregnant or breastfeeding.

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Condition: Metastasis From Malignant Tumor of Prostate (Disorder)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05653856

Sponsor: Curium US LLC

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. Patients with histologically proven prostate adenocarcinoma.
2. Prior radical prostatectomy or radiation therapy with curative intent.
3. Recurrence of disease defined as:
4. Prior Radical Prostatectomy: PSA > 0.2 ng/mL, or
5. Prior Radiation Therapy: 2 ng/mL rise in PSA over post-treatment nadir
6. Patients with at least one extraprostatic site of disease suspected based on prior imaging or diagnosed by biopsy.
7. Age greater than or equal to 18 years.
8. Able to understand and provide signed written informed consent.

Exclusion Criteria:

1. Androgen deprivation therapy (ADT) or other therapies targeting the androgen pathway, unless subject has a rising PSA level.
2. Body weight greater than 350 lb (158 kg).
3. Investigational therapy within the past 30 days.
4. Creatinine clearance (ClCr) less than 30 mL/min.
5. Participants who are capable of fathering a child and who are unwilling to take precautions to prevent pregnancy.

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Condition: Metastasis From Malignant Tumor of Prostate

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05204927

Sponsor: Curium US LLC

Phase: Phase 3

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. Male 18 years or older able to understand and provide signed written informed consent.
2. Histologically or pathologically confirmed prostate adenocarcinoma without predominant small cell component.
3. Progressive disease by one or more of the following criteria:
4. Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week apart with a minimum start value of >2 ng/mL.
5. Progression of measurable disease (RECIST 1.1) or presence of at least two new bone lesions (PCWG3 criteria).
6. Previous treatment with next-generation androgen receptor (AR)-directed therapy (e.g. abiraterone, enzalutamide, apalutamide, darolutamide).
7. Must have received no more than one previous AR-directed therapy.
8. Must have been administered ARAT (abiraterone, enzalutamide, darolutamide, or apalutamide) in the castration-sensitive or castration-resistant setting.
9. Must have progressed while on ARAT.
10. PSMA-PET scan (e.g., 68Ga-PSMA-11 or 18F-DCFPyL) positive as determined by central reader.
11. Effective castration with serum testosterone level of <50 ng/dL and plan to continue with chronic medical or surgical castration.
12. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
13. Patients with HIV that are healthy and with a low risk of acquired immune deficiency syndrome related outcomes may participate in the trial at the investigators' discretion.
14. Patients with HBV and HCV may also participate if symptoms are sufficiently managed.
15. Life expectancy of at least 6 months as assessed by investigator.
16. Willing to initiate ARAT therapy determined by investigator.
17. For patients who have partners of childbearing potential: The patient and/or partner must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 6 months after the last study drug administration.

Exclusion Criteria:

1. Prior treatment with radioligand therapy including other lutetium-labeled compounds.
2. Prior treatment with radium-223 (Xofigo) within the past 12 weeks.
3. Prior chemotherapy treatment for castration-resistant prostate cancer. Prior docetaxel use in the hormone-sensitive setting is permitted, as long as no more than 6 doses were received, the last dose was administered >1 year prior to consent, and disease progression did not occur during docetaxel treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2
5. Patients with known HRR gene-mutation (BRCA 1/2 encompassing both germline and somatic) who have not been previously treated with olaparib or rucaparib.
6. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
7. Inadequate organ and bone marrow function as evidenced by:
8. Hemoglobin < 8 g/dL.
9. Absolute neutrophil count < 1.5 x 109/L.
10. Platelet count < 100 x 109/L.
11. AST/SGOT and/or ALT/SGPT > 3.0 x ULN.
12. Total bilirubin > 2 x ULN unless patient has known Gilbert's syndrome and then may be 3 x ULN.
13. Creatinine clearance (CrCl) < 50 mL/min based on the Cockcroft-Gault equation.
14. Albumin ≤ 2.75 g/dL
15. Patients who undergo a transfusion for the sole purpose of meeting eligibility for this trial will be excluded.
16. Assessment by the Investigator as unable or unwilling to comply with the requirements of the protocol.
17. Use of an investigational therapeutic drug within the last 4 weeks prior to start of study treatment or scheduled to receive one during the study period.
18. Known CNS metastasis unless received therapy, asymptomatic and neurologically stable.
19. Patients receiving zoledronic acid for bone-targeted therapy must be on stable dose for 4 weeks prior to randomization.
20. Major surgery within 30 days of randomization as determined by the Investigator.
21. Patients with active significant cardiac disease defined by any of the following:
22. New York Heart Association class 3 or 4 congestive heart failure within 6 months of signing the ICF unless treated with improvement.
23. Current diagnosis of electrocardiogram abnormalities with significant cardiac arrhythmias
24. History of long QT syndrome or know history of Torsades de Pointe
25. History of myocardial infarction, angina pectoris, or coronary artery bypass graft within 6 months of ICF signature
26. Participants with symptomatic cord compression or clinical/radiological findings indicating impending spinal cord compression
27. Patients with a superscan seen on baseline bone scan as determined by investigator.
28. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer
29. Previous use of G-CSF for persistent neutropenia after standard of care treatment.
30. Participants who have a pregnant partner or are capable of fathering a child and who are unwilling to take precautions to prevent potential harm to the fetus or prevent pregnancy.
31. Participants with active Covid
32. Recovered patients may be included when completely recovered (no symptoms at least 28 days before study medication and a negative Covid test within 72 hours).

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Condition: Prostate Cancer, Advanced Prostate Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05396872

Sponsor: University of California, San Francisco

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Patient-participants: 1. Age 18 years or older. 2. Able to understand study procedures and to comply with them for the entire length of the study. 3. Able to understand a written informed consent document and willing to sign it. 4. Able to speak, read, and understand English. 5. Documentation of locally advanced (pelvic lymph node-positive), metastatic, or castration-resistant prostate cancer in a clinical progress note or pathology report. 6. Scheduled to attend a hematology/oncology appointment (in person or remote) during which provider anticipates discussing germline testing, somatic tumor testing, or targeted therapy. Caregiver-participants: 1. Age 18 years or older. 2. Identified by a patient-participant as an individual who is involved with the patient's care, and willing to join the interviews. 3. Able to provide verbal consent. 4. Able to speak and understand English. Provider-participants: 1. Hematology/oncology or Genetics provider (medical doctor (MD) or nurse practitioner (NP), post-first year clinical fellows allowed). 2. Has discussed germline testing, somatic testing, or targeted therapy for an San Francisco Veteran Health Care System (SFVAHCS) patient with locally advanced or metastatic prostate cancer (as defined above) within the past 90 days of being contacted about the study. 3. Able to provide consent via email. Stage 2: Inclusion Criteria: Patient participants: 1. Participated in Stage 1. 2. Completed either germline or tumor testing for prostate cancer. 3. Able to understand study procedures and to comply with them for the entire length of the study. Caregiver-participants: 1. Participated in Stage 1. 2. Partner, family-member, or friend of a Stage 2 participant (identified by the patient-participant as a caregiver). SFVAHCS Provider-participants: 1. Participated in Stage 1. 2. Meets one of the two following criteria:
• Physician specializing in medical oncology (MD, post-first year clinical fellows allowed) who has discussed genetic testing or targeted therapy with a patient with advanced prostate cancer within the past 30 days of being contacted for this study.
• Physician specializing in genetics who has discussed genetic testing or targeted therapy with a patient with advanced prostate cancer within the past 90 days of being contacted for this study. Non-SFVAHCS provider-participants: 1. Meets one of the three following criteria:
• Principal investigator of a Precision Oncology Program for Cancer of the Prostate (POPCaP) site.
• Physician specializing in medical oncology who has discussed genetic testing or targeted therapy with a patient with advanced prostate cancer within the past 30 days of being contacted for this study.
• Physician specializing in genetics who has discussed genetic testing or targeted therapy with a patient with advanced prostate cancer within the past 90 days of being contacted for this study. Note: For Non-SFVAHCS providers, fellows are not eligible. 2. Able to understand study procedures and to comply with them for the entire length of the study. Stage 3: Inclusion Criteria Patient-participants 1. Age 18 years or older. 2. Able to understand study procedures and to comply with them for the entire length of the study. 3. Able to understand a written informed consent document and willing to sign it. 4. Able to speak, read, and understand English. 5. Documentation of high-risk localized, very high-risk localized, locally advanced (pelvic lymph node-positive), metastatic, or castration-resistant prostate cancer in a clinical progress note or pathology report. 6. Scheduled to attend a hematology/oncology appointment (in person or remote) during which provider anticipates discussing germline testing. Caregiver-participants 1. Age 18 years or older. 2. Identified by a patient-participant as an individual who is involved with the patient's care, and willing to join the interview. 3. Able to provide verbal consent. 4. Able to speak and understand English. Provider-participants 1. SFVAHCS physician (MD) trained in medical oncology or undergoing training as a clinical fellow. 2. Has discussed germline testing for prostate cancer with an SFVAHCS patient within the past year of being contacted about the study, or plans to discuss germline testing for prostate cancer with an SFVAHCS patient. 3. Able to provide verbal consent. Stage 1: Exclusion Criteria Patient-participants: 1. For patient-participants undergoing genetic testing, if results of the genetic tests have already been disclosed to the participant, they are not eligible. Caregiver and Provider-Participants 2. If they do not meet any of the inclusion criteria above. Stage 2: Exclusion Criteria 1. Participants who do not meet the inclusion criteria above. Stage 3

Exclusion Criteria:

1. Patient-participants:
2. For patient-participants undergoing genetic testing, if results of the genetic tests have already been disclosed to the participant, they are not eligible. Caregiver and Provider-Participants
3. If they do not meet any of the inclusion criteria above. Stage 2: Exclusion Criteria
4. Participants who do not meet the inclusion criteria above. Stage 3: Exclusion Criteria Patient-participants:
5. Prior receipt of germline testing.
6. Prior participation in Stage 1 for germline testing. Caregiver and Provider-Participants
7. If they do not meet any of the inclusion criteria above.

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Condition: Metastatic Prostate Cancer, Castration-resistant Prostate Cancer, Prostatic Neoplasm, Cancer of the Prostate, Progressive mCRPC

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03939689

Sponsor: Progenics Pharmaceuticals, Inc.

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. Male ≥ 18 years of age
2. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features at initial diagnosis
3. Castration-resistant prostate cancer, with serum testosterone ≤ 50 ng/dL at Screening
4. Radiographic evidence of metastatic disease prior to Randomization or up to 21 days prior to Screening
5. Disease progression on prior abiraterone therapy as defined by meeting at least one of the following criteria per the investigator:
6. PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart
7. Soft tissue disease progression defined by RECIST 1.1
8. Bone disease progression defined by two or more new lesions on bone scan
9. Planned to receive treatment with enzalutamide
10. Subjects who are ineligible or choose not to receive taxane-based chemotherapy based on personal preference or physician opinion. Examples of conditions that could make a patient ineligible or refuse to receive taxane-based chemotherapy, but would allow them to still be eligible to receive I-131-1095 include the following:
11. Poor performance status
12. Prior intolerance to cytotoxic agents
13. History of another malignancy suspected for recurrence or metastases
14. Other serious medical conditions such as symptomatic peripheral neuropathy CTCAE Grade 2 or higher; or clinically significant cardiovascular disease per the Investigator or treating physician
15. Subjects receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Randomization
16. ECOG performance status 0-2
17. If sexually active, agree to use a medically acceptable method of birth control or sexual abstinence from the time of dosing through 28 days after the last dose of I-131-10
18. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.
19. Estimated life expectancy of at least 6 months as determined by the Investigator.
20. Able and willing to provide signed informed consent and comply with protocol requirements

Exclusion Criteria:

1. Received any anti-tumor therapy within 4 weeks of Randomization, with the exception of abiraterone, GnRH therapy and non-radioactive bone-targeted agents
2. Received prior chemotherapy for castration-resistant prostate cancer
3. Superscan as evidenced on baseline bone scan
4. Treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 within 6 months prior to Randomization
5. Prior hemi-body irradiation
6. Prior PSMA-targeted radioligand therapy
7. Major surgery within 4 weeks of Randomization
8. Impaired organ function as evidenced by the following laboratory values at Screening:
9. Absolute neutrophil count < 1500 μL
10. Platelet count < 100,000/μL
11. Hemoglobin < 9.5 g/dL
12. Albumin < 3.0 g/dL (30 g/L)
13. Total bilirubin > 2 x ULN unless in instances of known or suspected Gilbert's disease
14. AST or ALT > 2.5 x ULN
15. Calculated creatinine clearance (CrCL) < 30 mL/min (Cockroft-Gault equation), or currently on renal dialysis.
16. QT interval corrected for heart rate (QTc) > 470 msec
17. Previous use of enzalutamide for more than 7 days prior to consent
18. Planned initiation of alternative therapy for prostate cancer, investigational therapy, or participation in clinical trials during the study
19. History or risk of seizure (i.e., clinically significant neurological disorder) or any other condition that contraindicates treatment with enzalutamide
20. Gastrointestinal disorder affecting absorption of oral medications
21. Known or suspected brain metastasis or active leptomeningeal disease
22. Active malignancy other than prostate cancer, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or non-muscle invasive bladder/urothelial cancer
23. Subjects with any medical condition or other circumstances that, in the opinion of the investigator, compromise obtaining reliable data, achieving study objectives, or completing the study.

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Condition: Prostatic Neoplasms, Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06136598

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Exclusion Criteria:

1. include but are not limited to the following:

Inclusion Criteria:

• Has histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology.
• Has prostate cancer while receiving androgen deprivation therapy (ADT), or post-bilateral orchiectomy, within 6 months before screening.
• Has evidence of progression >4 weeks since last flutamide treatment or >6 weeks since last bicalutamide or nilutamide treatment.
• Has evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue shown by CT/MRI.
• Has disease that progressed during or after treatment with at least 1 line of next-generation hormonal agents (NHAs) for hormone-sensitive prostate cancer (HSPC) or castration-resistant prostate cancer (CRPC) for at least 8 weeks (at least 14 weeks for participants with bone progression).
• Has received at least 1 line of taxane-based chemotherapy for HSPC or CRPC and have had progressed disease during or on treatment, or refused or ineligible to receive chemotherapy.
• Has a life expectancy of >3 months. Exclusion Criteria:
• Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
• Has presence of gastrointestinal condition, e.g. malabsorption, that might affect the adsorption of study intervention.
• Has a history of pituitary dysfunction.
• Has poorly controlled diabetes mellitus.
• Has active or unstable cardio/cerebro-vascular disease, including thromboembolic events.
• Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 4 weeks of the date of allocation.
• Has received an anticancer monoclonal antibody (mAb) within 4 weeks of allocation, or has not recovered from adverse events (AEs) due to mAbs administered more than 4 weeks before the date of allocation.
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before the date of allocation.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any form of immunosuppressive therapy within 7 days prior to the start of study intervention.
• Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• Has a history of or current human immunodeficiency virus (HIV) infection.
• Has a concurrent Hepatitis B or Hepatitis C virus infection.
• Has a history of allogenic tissue or solid organ transplant.

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Condition: Prostatic Neoplasms, Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06104449

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Exclusion Criteria:

1. include but are not limited to the following:

Inclusion Criteria:

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nmol/L)
• Participants receiving bone anti-resorptive therapy (including, but not limited to bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks prior to the start of study intervention.
• Has progressed on or after treatment with at least 1 line of NHAs in metastatic hormone-sensitive prostate cancer (mHSPC) or in castration-resistant prostate cancer (CRPC) for a minimum of 12 weeks (e.g. abiraterone, enzalutamide, darolutamide, apalutamide), and with at least 1 line of taxane-based chemotherapy in mHSPC or in CRPC, or ineligibility for chemotherapy
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to allocation
• If capable of producing sperm, participant must agree to the following during the study treatment period and for at least 7 days after the last dose of opevesostat: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom. Exclusion Criteria:
• Has a history of pituitary dysfunction
• Has brain metastases
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
• Has an active or uncontrolled autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
• Has an active infection or other medical condition that would make corticosteroid contraindicated
• Has serious persistent infection within 2 weeks prior to the start of the study intervention
• Participants on an unstable dose of thyroid hormone therapy within 6 months prior to the start of the study intervention
• Has poorly controlled diabetes mellitus
• Hypotension: systolic blood pressure (BP) < 110 mmHg, or uncontrolled hypertension: systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg, in 2 out of 3 recordings with optimized antihypertensive therapy
• Has active or unstable cardio/cerebro-vascular disease, including thromboembolic event
• Is unable to swallow orally administered medication or known gastrointestinal (GI) disease or GI procedure that may interfere with absorption of study intervention
• Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to the start of the study intervention and not adequately recovered from the toxicities and/or complications
• Has received aldosterone antagonist (e.g. spironolactone, eplerenone) and phenytoin within 4 weeks prior to the start of the study intervention
• Has received radiotherapy within 4 weeks prior to the start of the study intervention, or radiation related toxicities, requiring corticosteroids
• Has received chemotherapy within the last 4 weeks (2 weeks for oral or weekly chemotherapy; 6 weeks for nitrosoureas and mitomycin C) prior to the start of the study intervention
• Has received prior enzalutamide and apalutamide within 3 weeks, or abiraterone and darolutamide within 2 weeks prior to the start of the study intervention
• Systemic use of the following medications within 2 weeks prior to the start of study intervention: strong cytochrome P450 (CYP)3A4 inducers: e.g., carbamazepine, rifampicin, phenobarbital, phenytoin, St John's Wort) and strong CYP3A4 inhibitors: e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, grapefruit juice
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
• Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto) within 4 weeks prior to the start of the study intervention
• Has received treatment with 5-α reductase inhibitors (eg, finasteride or dutasteride), estrogens, and/or cyproterone within 4 weeks prior to the start of the study intervention
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• History of human immunodeficiency virus (HIV) infection
• Has a history of Hepatitis B or active Hepatitis C virus
• Has a "superscan" bone scan
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the start of the study intervention

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Condition: Prostatic Neoplasms, Castration-Resistant, Neoplasms by Histologic Type, Neoplasms, Prostate, Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, Neoplasms, Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Prostatic Disease, Salivary Gland Cancer, Salivary Gland Tumor, Adenoid Cystic Carcinoma, Salivary Duct Carcinoma, Mucoepidermoid Carcinoma, Acinic Cell Tumor

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04249947

Sponsor: Poseida Therapeutics, Inc.

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Subjects ≥18 years of age
• Must have a confirmed diagnosis of mCRPC or SGC
• Must have measurable disease by RECIST 1.1 or bone only metastases with measurable PSA (≥1 ng/mL) (mCRPC subjects only)
• Must have progressed by PCWG3 and/or RECIST 1.1 (mCRPC subjects only)
• Must be willing to practice birth control from screening and for 2 years after the last administration of P-PSMA-101
• Must have adequate vital organ function within pre-determined parameters
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Exclusion Criteria:

• Has inadequate venous access and/or contraindications to leukapheresis
• Has an active second malignancy in addition to mCRPC or SGC, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma
• Has a history of or active autoimmune disease
• Has a history of significant central nervous system (CNS) disease, such as stroke or epilepsy
• Has an active systemic (viral, bacterial or fungal) infection
• Has received anti-cancer medications (excluding GnRH targeted therapies) within 2 weeks of the time of initiating conditioning chemotherapy
• Has received immunosuppressive medications (including anti-cancer medications) within 2 weeks of initiating leukapheresis and/or expected to require them while enrolled in the study
• Has received systemic corticosteroid therapy within 2 weeks of either the required leukapheresis or is expected to require it during the course of the study
• Has CNS metastases or symptomatic CNS involvement
• Has a history of significant ocular disease
• Has a history of significant liver disease or active liver disease
• Has liver metastases (<5 lesions and maximum diameter
• Has a history of or known predisposition to HLH or MAS

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Condition: Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06318273

Sponsor: AbbVie

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
• Estimated life expectancy > 6 months.
• Must have progressed on prior novel hormonal agents (NHAs) (e.g., abiraterone acetate and/or enzalutamide) for the treatment of metastatic prostate cancer and/or castration-resistant prostate cancer (CRPC). Determination of progression is done per local investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and/or Prostate Cancer Working Group 3 (PCWG3).
• Serum testosterone levels <= 50 ng/dL (<= 1.73 nmol/L) within the screening period and prior to the first dose of the study drug.
• Must have received at least one NHA (e.g., enzalutamide and/or abiraterone). Additionally, participants must have received at least one taxane for prostate cancer (or have refused, or are intolerant to, or unable to get access to taxanes).
• Must have >= 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging obtained <= 28 days prior to beginning study therapy.
• Serum prostate specific antigen (PSA) level >= 1.0 ng/mL.
• Availability of representative baseline tumor tissue (most recent archived tumor tissue after any novel hormonal agent (NHA) and/or any Prostate-Specific Membrane Antigen (PSMA) targeted therapy or fresh biopsy collected during screening phase) suitable for immunohistochemistry (IHC) testing. This requirement may be waived at the discretion of the AbbVie Medical Monitor if collecting a biopsy at screening would place the subject at risk of harm or would require a technically complicated procedure based on tumor location as assessed by the investigator.
• Laboratory values meeting the criteria laid out in the protocol.
• QT interval corrected for heart rate (QTc) < 470 msec (using Fridericia's correction), no >= Grade 3 arrythmia, and no other clinically significant cardiac abnormalities.

Exclusion Criteria:

• Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
• History of other active malignancy, as laid out in the protocol.
• History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, nor any evidence of active ILD or pneumonitis on screening chest CT scan.
• History of or active idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.
• History of or active clinically significant, intercurrent lung-specific illnesses including, but not limited to those listed in the protocol.

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Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06052306

Sponsor: Bayer

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• mCRPC with pathological confirmation of adenocarcinoma without small-cell or neuroendocrine features.
• Previous treatment with at least 1 Novel androgen axis drug (NAAD) (e.g., enzalutamide, apalutamide, darolutamide and/or abiraterone).
• Prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).
• Prior taxane treatment:
• Dose Escalation: Participants must either have had prior treatment with at least 1 but no more than 2 taxane regimens, or been deemed ineligible for or refused taxane therapy on consultation with their physician
• Dose Expansion Group A: Participants must have had prior treatment with at least 1 but no more than 2 taxane regimens, in the castration-resistant setting
• Dose Expansion Group B: Participants must not have received taxane therapy since becoming castration-resistant
• Dose Expansion Group C: Participants must either have had prior treatment with at least 1 but no more than 2 taxane regimens, or been deemed ineligible for or refused taxane therapy on consultation with their physician
• Prior treatment with 177Lu-PSMA is required for participants in Dose Expansion Group C only.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• Adequate bone marrow, hepatic, and renal function, as assessed by the following laboratory requirements within 28 days before start of study treatment:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1500/mm^3
• Platelet count ≥100,000/mm^3
• Total bilirubin ≤1.5 x the Upper limit of normal (ULN), except if confirmed history of Gilbert's disease
• Alanine transaminase (ALT) and Aspartate transaminase (AST) ˂2.5 x ULN (≤5 x ULN for participants with liver involvement)
• Participants on a stable dose of anticoagulation therapy are allowed to participate if they have no sign of bleeding or clotting, and Prothrombin time international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) test results are acceptable at the Investigator's discretion
• Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m^2, according to the Modified Diet in Renal Disease (MDRD) abbreviated formula and creatinine clearance (CrCl) >60 mL/min based on Cockcroft-Gault formula
• Participants must have at least one Prostate-specific membrane antigen (PSMA)-positive distant metastatic lesion on the screening PSMA PET/CT scan using the study-designated PSMA PET tracers, as determined by the site Investigator. For eligibility purposes, a PSMA-positive lesion must have activity greater than the liver by visual assessment of the screening PSMA PET/CT. A PSMA-positive metastatic lesion should not correspond to a normal tissue structure or benign lesion.

Exclusion Criteria:

• Participants who have any of the following tumor lesions which are PSMA negative AND meet the size criteria below are excluded as determined by the site investigator. A PSMA-negative lesion for eligibility purposes must have activity equal to or less than the liver by visual assessment of the screening PSMA PET/CT scan using the study-designated PSMA PET/CT tracers. A PSMA-negative metastatic lesion should not correspond to a normal tissue structure or benign lesion.
• a. Any single or multiple lymph node(s) ≥2.5cm in the short axis.
• b. Any solid organ metastasis (e.g., lung, liver, adrenal glands, etc.) that is ≥1 cm in the short axis.
• c. Any bone metastasis with a soft tissue component ≥ 1cm in short axis with the soft tissue component being PSMA-negative. PSMA-negative osseous metastases without a soft tissue component do not exclude a participant.
• d. Predominantly necrotic lesions with greater than 1cm of enhancing tissue on contrast-enhanced Computer tomography / magnetic resonance imaging (CT/MRI).
• Prior systemic anticancer therapy including chemotherapy, NAAD, biologic therapy, immunotherapy, or investigational therapies within 4 weeks of the start of study treatment, except luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH). Start of study treatment is allowed in shorter timeframes if 5 half-lives of the prior drug(s) have elapsed.
• Prior radiopharmaceutical treatment using 225Ac.
• Other prior radiopharmaceutical treatments:
• Dose escalation and Dose expansion Groups A and B: Prior treatment with a radiopharmaceutical is prohibited.
• Dose expansion Group C: Prior treatment with a radiopharmaceutical is prohibited with the following exceptions: Prior treatment with radium-223 dichloride more than 3 months before the start of study treatment is permitted; and prior treatment with 177Lu PSMA more than 6 weeks before the start of study treatment is required.
• Prior definitive therapy (radiotherapy or surgery) completed less than 6 weeks before the start of study treatment. Note that palliative radiotherapy completed less than 6 weeks before the start of study treatment will be allowed if: (i) no more than 10% of the participants' bone marrow is irradiated, (ii) it does not encompass all potential target/measurable lesions for participants in dose expansion.
• Toxic effects of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 from prior anticancer therapy not yet stabilized or where significant post-treatment toxicities have been observed. Chronic toxic effects of CTCAE Grade ≤2 from prior anticancer therapy where no further resolution is expected do not require exclusion with agreement between the Investigator and Sponsor (e.g., chemotherapy-induced neuropathy, fatigue, alopecia, anorexia, etc.).

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Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04227275

Sponsor: Tmunity Therapeutics

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Confirmed histologic diagnosis of prostate cancer and have mCRPC, with castrate levels of testosterone (<50 ng/mL)
• PSA measurable disease per Prostate Working Group 3 (PCWG3) criteria
• Prior therapies defined as at least 2 prior lines of systemic therapy for prostate cancer, including at least one second generation androgen receptor inhibitor and/or CYP17α inhibitor. At least one line of prior therapy must be in the mCRPC setting
• Estimated estimated glomerular filtration rate ≥ 60 mL/min by Modification of Diet in Renal Disease criteria
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x the upper limit of normal (ULN); patients with hepatic metastases ALT and AST ≤ 3.0 x ULN
• Serum total bilirubin < 1.5 mg/dL unless patient has known Gilbert's Syndrome, then serum bilirubin ≤3 mg/dL
• Serum albumin ≥ 3.0 g/dL
• Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have been performed within 8 weeks of enrollment
• Hemoglobin ≥ 8 g/dL
• Absolute neutrophil count ≥ 1000/μL
• Platelet count ≥ 75,000/μL
• Patients who have not undergone bilateral orchiectomy must be able to continue gonadotropin-releasing hormone (GnRH) therapy during the study
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• Toxicities from any previous therapy must have recovered to Grade 1 or baseline
• Patients of reproductive potential agree to use of approved highly effective contraceptive methods

Exclusion Criteria:

• Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to screening, unless treated with curative intent
• Current treatment with systemic corticosteroids (defined as a dose greater than the equivalent of prednisone 10 mg/day)
• Active autoimmune disease (including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease or multiple sclerosis) or a history of severe autoimmune disease requiring prolonged immunosuppressive therapy (any immunosuppressive therapy within 6 weeks prior to screening visit)
• Current human immunodeficiency virus (HIV), hepatitis C virus, hepatitis B virus infections; Patients who are hepatitis B core antigen positive, hepatitis B surface antigen negative, should have a quantitative viral load measured; If viral load is undetectable, the patient will not be excluded if hey are able to be treated with anti-viral medication for at least 7 days prior to lymphodepletion until at least 6 months after infusion with viral load and ALT monitoring
• Active or uncontrolled medical or psychological condition that would preclude participation
• History of seizure disorder
• Prior allogeneic stem cell transplant
• Central nervous system malignancy
• History of severe infusion reaction to monoclonal antibodies or biological therapies, or to study product excipients that would preclude the patient safely receiving CART-PSMA-TGFβRDN cells
• History of being previously treated with a J591 antibody-based therapy
• Ferritin levels ≥ 4x the upper limit of normal prior to apheresis or prior to the start of lymphodepleting chemotherapy
• Active or recent (within the past 6 months prior to apheresis or lymphodepletion) cardiovascular disease, defined as (1) New York Heart Association Class III or IV heart failure, (2) unstable angina, (3) a history of recent (within 6 months) myocardial infarction or sustained (> 30 second) ventricular tachyarrhythmias, or (4) cerebrovascular accident
• Any active infection currently being treated or any infection within the last 6 weeks that required 7 days or more of IV antibiotics or any active infection within the last 4 weeks that requires use of oral antibiotics. Patients may be eligible once these timeframes elapse and with evidence that the infection has completely resolved
• Have inadequate venous access for or contraindications for the apheresis procedure
• Must agree not to participate in a conception process or must agree to a highly effective method of contraception

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Condition: Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02711956

Sponsor: Zenith Epigenetics

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. Males age ≥ 18 years
2. Metastatic, castrate resistant, histologically confirmed prostate cancer; surgically castrated or continuous medical castration for ≥ 8 weeks prior to screening
3. Serum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drug
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Adequate laboratory parameters [absolute neutrophil (ANC), platelets, asparate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and coagulation parameters] at screening
6. Dose Escalation only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone
7. Dose Confirmation Cohort A (DC-A) only: Currently receiving enzalutamide as most recent systemic therapy for mCRPC and have experienced PSA progression by PCWG2 criteria in the absence of radiographic and/or clinical progression. Patients may or may not have experienced prior progression on abiraterone.
8. Dose Confirmation Cohort B (DC-B) only: Enzalutamide-naïve patients following prior progression on abiraterone by PCWG2 criteria and within 12 weeks of discontinuing abiraterone

Exclusion Criteria:

1. Any history of brain metastases or prior seizure or conditions predisposing to seizure activity
2. Have previously received an investigational BET inhibitor (including previous participation in this study or Study ZEN003694-001)
3. Have received prior systemic anti-cancer therapy (including abiraterone) or investigational therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug
4. Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry
5. Radiation therapy within 2 weeks of the first administration of study drug
6. Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to study entry)
7. Have received prior investigational anti-androgen therapy, including ARN-509
8. Currently receiving medications known to be strong inhibitors of CYP2C8, strong inducers (except enzalutamide) or inhibitors of CYP3A4 and substrates of CYP3A4, CYP2C9 and CYP2C19 with a narrow therapeutic window. Strong inducers, inhibitors and substrates must be discontinued at least 7 days prior to the first administration of study drug.
9. Not a candidate for enzalutamide treatment, in the opinion of the Investigator

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Condition: Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02705469

Sponsor: Zenith Epigenetics

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. Males age ≥ 18 years
2. Metastatic, castrate resistant, histologically confirmed prostate cancer; surgically castrated or continuous medical castration for ≥ 8 weeks prior to screening
3. Serum testosterone < 50 ng/dL determined within 4 weeks of first administration of study drug
4. Prior progression on one or more androgen-receptor/androgen-synthesis inhibitor therapies (e.g. abiraterone, enzalutamide, apalutamide, TAK-700 and/or galeterone) by Prostate Cancer Working Group 2 (PCWG2) criteria. Prior progression on bicalutamide/nilutamide/flutamide/ketoconazole alone is not allowed.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Adequate laboratory parameters [absolute neutrophil (ANC), platelets, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and coagulation parameters] at screening

Exclusion Criteria:

1. Any history of brain metastases or prior seizure or conditions predisposing to seizure activity
2. Have previously received an investigational BET inhibitor (including previous participation in this study or Study ZEN003694-002)
3. Have received prior systemic anti-cancer therapy or investigational therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first administration of study drug
4. Failure to recover to Grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study entry
5. Radiation therapy within 2 weeks of first administration of study drug
6. Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to study entry)
7. Currently receiving medications known to be strong inducers or inhibitors of CYP3A4 with a narrow therapeutic window. Strong inducers and inhibitors of CYP3A4 with narrow therapeutic ranges must be discontinued at least 7 days prior to the first administration of study drug.

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Condition: Metastatic Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04786847

Sponsor: Telix International Pty Ltd

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum 80 Years
• Gender: Male

Inclusion Criteria:

• Be male, at least 18 years old, with histologically/pathologically confirmed metastatic adenocarcinoma.
• Be of ECOG Performance Status 0, 1, or 2 and have an estimated life expectancy of ≥ 6 months.
• Have metastatic disease (≥1 metastatic lesions present on baseline whole body CT, MRI, or bone scintigraphy).
• Have castration-resistant PC (defined as disease progressing despite castration by orchiectomy or ongoing use of luteinizing hormone-releasing hormone [LHRH] agonists) and must have a castrate level of serum/plasma testosterone (< 50 ng/dL or <1.7 nmol/L).
• In the mCRPC setting, must have received a minimum of 12 weeks of prior therapy with a NAAD, either enzalutamide or abiraterone plus prednisone.
• Have received one line of prior taxane therapy, or have refused or are ineligible for taxanes
• Have disease that is progressing at study entry, despite a castrate testosterone level (<50 ng/dL or <1.7 nmol/L), by the demonstration of at least one of the following: 1. Increase in PSA greater than 25% and > 2 ng/mL above nadir, confirmed by progression at 2 timepoints at least 3 weeks apart. 2. Progressive disease or new lesion(s) (relative to previous imaging) in the viscera or lymph nodes as per RECIST1.1 or in bone as per Prostate Cancer Working Group 3 [PCWG3). Any ambiguous results are to be confirmed by additional imaging modality (e.g., CT, Tc-99m bone scintigraphy)
• Have disease which is PSMA positive, as demonstrated by a 68Ga-PSMA-11 PET/CT or [18F]DCFPyL PET/CT scan and confirmed as eligible by local reader (patient must have at least one site of metastatic disease with SUVmax ≥1.5 times the SUV of normal liver). If the disease meets the criteria for PSMA positivity, but there is one or more soft tissue lesion of ≥2 cm that is not PSMA positive, then the patient is to be excluded on the grounds that there is substantial disease which might not respond to the therapy.
• Must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e., surgery, local radiotherapy, NAAD, chemotherapy, etc.).
• Can be receiving a bisphosphonate or denosumab regimen provided tolerance to this therapy has been proven. 11. Have adequate organ function at Screening: a. Bone marrow: i. Platelets ≥150×109/L ii. Absolute neutrophil count >1.5×109/L iii. Hemoglobin ≥10g/dL (no red blood cell transfusion in the previous 4 weeks) b. Liver function: i. Total bilirubin ≤1.5×the upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3×ULN is permitted ii. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3×ULN OR ≤5×ULN for patients with liver metastases c. Renal function: i. Serum/plasma creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min
• Have the capacity to understand the study and be able and willing to comply with all protocol requirements.
• Must comply with the radiation protection guidelines (including hospital admissions and isolation) that are applied by the treating institution in order to protect their contacts and the general public.
• Must agree to practice adequate precautions to prevent pregnancy in a partner and to avoid potential problems associated with radiation exposure to the unborn child (Refer to Clinical Trials Facilitation Group, 2020: Recommendations related to contraception and pregnancy testing in clinical trials Version 1.1, CTFG, 2020). Exclusion:
• Are unable, in the opinion of the Investigator, to understand or are unwilling to sign a written informed consent document or to follow investigational procedures.
• Have PC with pathological findings consistent with small cell or any histology other than adenocarcinoma of the prostate. If there are minor elements of neuroendocrine histology, this is acceptable.
• Experiencing uncontrolled pain
• Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with a prior history of malignancy that has been adequately treated and who have been disease-free for more than 3 years are eligible, as are patients with adequately treated non-melanoma skin cancer, and superficial bladder cancer.
• At increased risk of hemorrhage, or with a recent history of a thrombotic event (e.g., deep vein thrombosis [DVT]/ pulmonary embolism [PE]) and/or are using long-term anti-coagulant or anti-platelet agents.
• Have received prior administration of monoclonal antibody (mAb) J591 or HuJ591 or any other PSMA targeted therapy.
• Have known allergies, hypersensitivity, or intolerance to the investigational drug or its excipients.
• Have received systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy, or biological therapy) and/or radiation therapy within 4 weeks of enrollment OR if any significant AEs have not resolved to National Cancer Institute (NCI) AE Criteria ≤2; OR are receiving other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
• Have received prior treatment with radiopharmaceuticals containing, but not limited to, the following radioisotopes: 89Strontium, 153Samarium, 186Rhenium, 188Rhenium, 223Radium; or have received hemi-body irradiation within 6 months prior to randomization.
• Have received other investigational agents within 4 weeks of randomization.
• Have known brain metastases (any size) or hepatic metastases > 1 cm.
• Have a history of seizure and/or stroke within past 6 months.
• Have clinical or radiologic findings indicative of impending cord compression or experiencing symptomatic cord compression.
• Have a serious active or sub-clinical infection, or angina pectoris or heart failure (New York Heart Association [NYHA] Class III or IV), significantly prolonged QT interval or other serious illness(es) involving the cardiac, respiratory, central nervous, renal, hepatic or hematological organ systems, which might impair the ability to complete this study or could interfere with determination of causality of any adverse effects experienced in this study, or which require treatment that could interact with study treatment.
• Have received treatment with any PARP inhibitors (i.e., Olaparib) or with any platinum based anti-neoplastic drugs.
• Have a known alteration in breast cancer genes (BRCA) BRCA1, BRCA2, or Ataxia Telangiectasia Mutated Gene (ATM) gene and are eligible to receive Olaparib therapy according to their treating institution SoC.

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Condition: Metastatic Castration-resistant Prostate Cancer, Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03792841

Sponsor: Amgen

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Subject has provided informed consent prior to initiation of any study specific activities/procedures
• Subjects with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Progression on novel antiandrogen therapy may have occurred in the non-metastatic CRPC setting
• Subjects must have undergone bilateral orchiectomy or must be on continuous ADT with a gonadotropin releasing hormone (GnRH) agonist or antagonist
• Total serum testosterone
• Evidence of progressive disease, defined as 1 or more PCWG3 criteria:
• PSA level >/= 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart
• nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications
• appearance of 2 or more new lesions in bone scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0
• 1
• Life expectancy >/= 6months

Exclusion Criteria:

• Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone agonist (LHRH)/GnRH analogue (agonist/antagonist). Subjects on a stable bisophosphonate or denosumab regimen for >/= 30 days prior to randomization are eligible
• Prior PSMA-targeted therapy (subjects on prior therapy may be eligible if discussed with Amgen medical monitor prior to enrollment)
• Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
• Active autoimmune disease or any other diseases requiring immunosuppressive therapy while on study
• Needing chronic systemic corticosteroid therapy (prednisone > 10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-tumor necrosis factor alpha [TNF alpha] therapies) unless stopped 7 days prior to start of first dose
• Myocardial infarction, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of acapatamab Part 2 only:
• Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a Grade 3 or higher immune-related adverse event prior to first day of dosing
• History or evidence of interstitial lung disease or active, non-infectious pneumonitis Part 3 only:
• Evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product Part 6 only: Subjects are excluded from this cohort if any of the following additional criteria apply:
• Subjects taking strong OAT3 inhibitors (eg, probenecid) or adjust the dosing to 1 mg PO QD.
• Subjects with latent or active tuberculosis at screening

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02202447

Sponsor: Endocyte

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Patients must have the ability to sign an approved informed consent form (ICF).
• Patients must be ≥ 18 years of age.
• Patients must have histological, pathological and/or cytological confirmation of prostate cancer.
• Patients must have progressive, metastatic, castration-resistant prostate cancer (mCRPC) as defined below:
• Documented progressive metastatic CRPC will be based on at least one of the following criteria:
• PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL.
• Soft-tissue progression defined as an increase ≥ 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions.
• Progression of bone disease (evaluable disease) or (new bone lesion(s)) by bone scan.
• Patients must have prior and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (<50 ng/dL).
• Patients must have progressed on abiraterone and/or enzalutamide.
• Patients must have been previously treated with a taxane except in cases of contraindication (e.g. poor performance status, age or patient choice)
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients must have at least one measurable lesion that can be followed for response assessment on baseline imaging obtained no more than 28 days prior to beginning study therapy. Baseline and follow up radiological disease assessment must include bone scans performed with either Technetium-99m labeled diphosphonates or Fluorine-18 sodium fluoride PET or PET/CT, as per the local standard of care for patients with prostate cancer.
• Patients with CNS metastases that are symptomatic must have received therapy (surgery, XRT, gamma knife) and be neurologically stable and off of steroids. The patient should be off steroids at least 14 days before pre-registration. Asymptomatic CNS metastatic disease without associated edema, shift, requirement for steroids or anti-seizure medications are eligible after discussion with the sponsor medical monitor. For patients with a history of CNS metastasis, baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)
• Patients must have recovered (to baseline/stabilization) from prior therapy-associated acute toxicities.
• Patients with prior radiation therapy are eligible if they meet the following criteria:
• Prior radiotherapy must be completed at least 4 weeks before patient begins study therapy.
• Patient must have recovered from the acute toxic effects of the treatment before beginning study therapy.
• Patients must have adequate organ function:
• Bone marrow reserve: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelets ≥ 100 x 109/L. Hemoglobin ≥ 9 g/dL.
• Cardiac:
• Left ventricular ejection fraction (LVEF) equal to or greater than the institutional lower limit of normal. LVEF must be evaluated within 28 days prior to beginning study therapy.
• Cardiac Troponin I within normal limit.
• Hepatic: Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN for patients with liver metastases.
• Renal: Serum creatinine ≤ 1.5 x ULN, or for patients with serum creatinine > 1.5 ULN, creatinine clearance ≥ 50 mL/min. Exclusion Criteria:
• More than 3 prior systemic anti-cancer therapies (e.g. cytotoxic agents, biologic agents) regimens for metastatic disease
• Previous treatment with Samarium-153 or Strontium-89.
• Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to beginning study therapy.
• Known hypersensitivity to the components of the study therapy or its analogs.
• Carcinomatous meningitis and/or symptomatic central nervous system (CNS) metastases.
• Malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with adequately treated non-melanoma skin cancer and patients with prior history of malignancy who have been disease free for more than 3 years are eligible.
• Neuropathy CTCAE grade > 2
• QTc interval of > 480 ms.
• History of ischemic cardiac disease that has occurred within 6 months prior to study entry.
• Any other serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension.
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy.
• Active uncontrolled infections
• Known active Hepatitis B or C infections Inclusion Criteria for Part B: To qualify for enrollment, the following criteria must be met: 1. Patients must have the ability to understand, and have signed an approved ICF 2. Patients must be males ≥ 18 years of age 3. Patients must have histological, pathological and/or cytological confirmation of prostate cancer 4. Patients must have progressive mCRPC defined by meeting at least one of the following criteria: 1. PSA progression defined as 25% increase over a baseline value of > 2 ng/ml with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1-week interval. Baseline is defined as the PSA nadir level since commencing most recent prior therapy 2. Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD; short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD, or the appearance of one or more new lesions, since the onset of the most recent prior therapy 3. Progression of bone disease according to PCWG3 criteria 5. Patients must have a castrate level of serum testosterone (< 50 ng/dL) 6. For inclusion in Cohort 1, mCRPC patients must have progressed while receiving (or subsequent to receiving) abiraterone and/or enzalutamide but must not have previously received taxane-based systemic chemotherapy for mCRPC (previous treatment with six cycles of docetaxel for metastatic castration-sensitive prostate cancer (mCSPC) is permissible). NOTE: patients receiving fewer than 2 cycles of taxane based regimen due to intolerance are eligible for cohort 1. 7. For inclusion in Cohort 2, mCRPC patients must have progressed while receiving (or subsequent to receiving) abiraterone and/or enzalutamide and must have progressed subsequent to receiving ≥ 2 cycles of a taxane-based regimen for mCRPC. 8. Patients must have a ECOG performance status of 0 or 1 9. Patients must have at least one metastatic lesion that can be followed on baseline imaging obtained no more than 28 days prior to beginning study therapy. Baseline and follow up radiological disease assessments must include bone scans performed with 99mTc labelled diphosphonates 10. Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast) 11. Patients must have recovered (to baseline/stabilization) from prior chemo- or radio-therapy and associated acute toxicities must have resolved to a NCI CTCAE v4 Grade 1 or less, with the exception of alopecia 12. Patients must have adequate organ function: a) Bone marrow reserve: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9 g/dL b) Cardiac: i) QTcF < 450 msec on at least 2 of 3 screening ECGs. On site determination of QTcF may be used for screening purposes ii) LVEF equal to or greater than the institutional lower limit of normal. LVEF must be evaluated within 7 to 10 days prior to beginning study therapy iii) Cardiac Troponin I within normal limit (as per local institution) c) Hepatic: Total bilirubin ≤ 1.5 x ULN, ALT, AST ≤ 3.0 x ULN OR ≤ 5.0 x ULN for patients with liver metastases d) Renal: Serum/plasma creatinine ≤ 1.5 x ULN, or for patients with serum/plasma creatinine > 1.5 ULN, creatinine clearance ≥ 50 mL/min

Exclusion Criteria:

• More than 3 prior systemic anti-cancer therapies (e.g. cytotoxic agents, biologic agents) regimens for metastatic disease
• Previous treatment with Samarium-153 or Strontium-89.
• Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to beginning study therapy.
• Known hypersensitivity to the components of the study therapy or its analogs.
• Carcinomatous meningitis and/or symptomatic central nervous system (CNS) metastases.
• Malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with adequately treated non-melanoma skin cancer and patients with prior history of malignancy who have been disease free for more than 3 years are eligible.
• Neuropathy CTCAE grade > 2
• QTc interval of > 480 ms.
• History of ischemic cardiac disease that has occurred within 6 months prior to study entry.
• Any other serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension.
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy.
• Active uncontrolled infections
• Known active Hepatitis B or C infections Inclusion Criteria for Part B: To qualify for enrollment, the following criteria must be met: 1. Patients must have the ability to understand, and have signed an approved ICF 2. Patients must be males ≥ 18 years of age 3. Patients must have histological, pathological and/or cytological confirmation of prostate cancer 4. Patients must have progressive mCRPC defined by meeting at least one of the following criteria: 1. PSA progression defined as 25% increase over a baseline value of > 2 ng/ml with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1-week interval. Baseline is defined as the PSA nadir level since commencing most recent prior therapy 2. Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD; short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD, or the appearance of one or more new lesions, since the onset of the most recent prior therapy 3. Progression of bone disease according to PCWG3 criteria 5. Patients must have a castrate level of serum testosterone (< 50 ng/dL) 6. For inclusion in Cohort 1, mCRPC patients must have progressed while receiving (or subsequent to receiving) abiraterone and/or enzalutamide but must not have previously received taxane-based systemic chemotherapy for mCRPC (previous treatment with six cycles of docetaxel for metastatic castration-sensitive prostate cancer (mCSPC) is permissible). NOTE: patients receiving fewer than 2 cycles of taxane based regimen due to intolerance are eligible for cohort 1. 7. For inclusion in Cohort 2, mCRPC patients must have progressed while receiving (or subsequent to receiving) abiraterone and/or enzalutamide and must have progressed subsequent to receiving ≥ 2 cycles of a taxane-based regimen for mCRPC. 8. Patients must have a ECOG performance status of 0 or 1 9. Patients must have at least one metastatic lesion that can be followed on baseline imaging obtained no more than 28 days prior to beginning study therapy. Baseline and follow up radiological disease assessments must include bone scans performed with 99mTc labelled diphosphonates 10. Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast) 11. Patients must have recovered (to baseline/stabilization) from prior chemo- or radio-therapy and associated acute toxicities must have resolved to a NCI CTCAE v4 Grade 1 or less, with the exception of alopecia 12. Patients must have adequate organ function: a) Bone marrow reserve: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9 g/dL b) Cardiac: i) QTcF < 450 msec on at least 2 of 3 screening ECGs. On site determination of QTcF may be used for screening purposes ii) LVEF equal to or greater than the institutional lower limit of normal. LVEF must be evaluated within 7 to 10 days prior to beginning study therapy iii) Cardiac Troponin I within normal limit (as per local institution) c) Hepatic: Total bilirubin ≤ 1.5 x ULN, ALT, AST ≤ 3.0 x ULN OR ≤ 5.0 x ULN for patients with liver metastases d) Renal: Serum/plasma creatinine ≤ 1.5 x ULN, or for patients with serum/plasma creatinine > 1.5 ULN, creatinine clearance ≥ 50 mL/min Exclusion Criteria for Part B: The presence of any of the following will exclude the patient from the study: 1. Previous treatment with Samarium-153, Strontium-89, Rhenium-186 or Radium-223 within 6 months of starting (i.e., Cycle 1 Day 1) EC1169 2. Any systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy or biological therapy (including monoclonal antibodies), or experimental anti-cancer therapy) within 28 days prior to beginning study therapy. Note: Ongoing castrating therapy with a GnRH agonist or antagonist is mandatory to assure a castrate level of serum testosterone <50 ng/dL, except in patients who have undergone an orchiectomy. Bisphosphonates or denosumab continuation is permissible (i.e., no change for 30 days prior to Cycle 1 Day 1). Patients who receive a dose of EC1169 under another Endocyte protocol do not need a washout period for EC1169 3. Known hypersensitivity to the components of the study therapy. (Please reference Section 1, Formulation of EC1169 and EC0652, in the respective Pharmacy Manuals) 4. Carcinomatous meningitis and/or symptomatic CNS metastases 5. Concurrent malignancies that are expected to alter life expectancy (e.g., NSCLC, etc.) or that may interfere with assessment of prostate cancer (e.g., lymphoma involving the periaortic nodes). Patients with adequately treated non-melanoma skin cancer or non-muscle invasive urothelial carcinoma, and patients with prior history of malignancy who have been disease-free for more than 5 years are eligible 6. Patients considered at risk for life-threatening QTc prolongation (i.e., personal or family history of Long QT syndrome, presence of implantable pacemaker, or implantable cardioverter defibrillator, etc.) 7. Use of the following medications within 6 months prior to EC1169 administration: amiodarone, disopyramide, dofetilide, dronedarone, flecanamide, ibutilide, quinidine, or sotalol 8. Any other serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension 9. Known systemic infections including, but not limited to hepatitis B or C, or HIV

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Condition: Prostate Cancer Metastatic

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03575819

Sponsor: Fortis Therapeutics, Inc.

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Male ≥ 18 years of age
• Has histologically confirmed prostate cancer that is metastatic and has progressed as defined by PCWG3 criteria during or after treatment with at least 1 ASI (eg, abiraterone, enzalutamide, apalutamide), or another second-generation anti-androgen or cytochrome P450 (CYP)17A1 inhibitor, with the most recent ASI administered in the castration-resistant setting
• Has serum testosterone levels < 50 ng/dL during screening. Patients without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analog during the course of protocol therapy
• ECOG performance status of 0 or 1
• Adequate hematologic, renal and hepatic function
• Males with female partners of childbearing potential must agree to use 2 effective methods of contraception
• Patients must provide signed informed consent
• Patients enrolled into the dose expansion phase must have prostate carcinoma without histologic evidence of small-cell/neuroendocrine carcinoma features on prior biopsy or must have unequivocal histologic evidence of small-cell/neuroendocrine prostate carcinoma (pure or mixed). Patients with treatment-emergent small-cell neuroendocrine cancer (pure or mixed) may have received no more than on prior chemotherapy regimen for mCRPC
• Patients enrolled into the dose expansion phase must be willing to undergo a metastatic tumor biopsy or has tissue available from a prior post-castration resistant tumor biopsy

Exclusion Criteria:

• Persistent clinically significant toxicities from previous anticancer therapy
• Has NCI CTCAE Grade ≥ 2 peripheral neuropathy from any etiology or has a genetic disorder that is associated with peripheral neuropathy even without current neuropathic manifestations
• Prior treatment with cytotoxic chemotherapy for mCRPC (chemotherapy in the hormone-sensitive setting is allowed if > 6 months before study entry)
• Has received external-beam radiation or systemic anticancer therapy within 14 days before first dose of FOR46
• Has received treatment with an investigational drug within 28 days before first dose of FOR46
• Has had a major surgical procedure within 28 days before administration of FOR46 dose
• Clinically significant cardiovascular disease
• Uncontrolled, clinically significant pulmonary disease
• Has a history of brain or leptomeningeal metastases.
• Uncontrolled intercurrent illness
• Has a known positive status for HIV or either active/chronic hepatitis B/C
• Requires medications that are strong inhibitors or strong inducers of CYP3A4
• [Dose escalation only] Has a history of episodic atrial fibrillation or flutter (patients with chronic atrial fibrillation are not excluded)

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Condition: Male Breast Carcinoma, Prostate Adenocarcinoma, Recurrent Breast Carcinoma, Recurrent Non-Small Cell Lung Carcinoma, Recurrent Prostate Carcinoma, Stage IV Breast Cancer, Stage IV Non-Small Cell Lung Cancer, Stage IV Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02206334

Sponsor: NRG Oncology

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Metastatic breast cancer (MBC) OR metastatic non-small cell lung cancer (NSCLC) OR metastatic adenocarcinoma of the prostate; the sites of allowed metastases are: peripheral lung, central lung, mediastinal/cervical lymph node, liver, spinal/paraspinal, osseous, and abdominal-pelvic
• NOTE: after the required number of evaluable patients have been accrued for a given dose level, the accrual for that metastatic location will be temporarily suspended while the safety of that dose level is assessed; a patient can only be entered onto the trial if all of their metastatic locations are open to accrual (e.g. if central lung is temporarily suspended for safety assessment and the patient has a central lung metastases, regardless of other metastases, they cannot enroll until the safety of dose to central lung is determined)
• Primary tumor site without progression at registration
• All metastases not resected must be amenable to SBRT
• The patient must meet ONE of the three following criteria:
• 3-4 radiographically distinct metastases of any distribution in the allowed anatomical sites OR
• 2 radiographically distinct metastases that must be anatomically close (i.e., with less than or equal to 5 cm of normal tissue between them) OR
• 3 or 4 distinct metastasis, 2 or 3 to be treated with SBRT and the other (s) having been surgically removed
• Evaluation by a radiation oncologist within 45 days prior to study registration
• Evaluation by a medical oncologist within 45 days prior to study registration
• The following imaging workup to document metastases within 45 days prior to study registration:
• Computed tomography (CT) scans of the chest, abdomen and pelvis with radionuclide bone scan OR whole body positron emission tomography (PET)/CT
• History/physical examination within 45 days prior to study registration
• Zubrod performance status =< 2 within 45 days prior to study registration
• Age >= 18 years
• Absolute neutrophil count (ANC) >= 500 cells/mm^3
• Platelets >= 50,000 /mm^3
• Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• If liver metastases present, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be < 3 x upper limit of normal (ULN)
• Patient must provide study specific informed consent prior to study entry
• For females of child-bearing potential, negative serum/urine pregnancy test within 14 days prior to study registration

Exclusion Criteria:

• Progression of primary tumor site (breast, prostate, or lung) at time of registration
• Metastases with indistinct borders making targeting not feasible
• Known brain metastases
• Prior palliative radiotherapy to metastases
• Metastases located within 3 cm of the previously irradiated structures:
• Spinal cord previously irradiated to > 40 Gy (delivered in =< 3 Gy/fraction)
• Brachial plexus previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)
• Small intestine, large intestine, or stomach previously irradiated to > 45 Gy (delivered in =< 3 Gy/fraction)
• Brain stem previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)
• Whole lung previously irradiated with prior volume 20 Gy (V20Gy) > 30% (delivered in =< 3 Gy/fraction)
• Primary tumor irradiated with SBRT
• Metastasis irradiated with SBRT
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration
• Transmural myocardial infarction within the last 6 months prior to registration
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
• Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease
• Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD) 4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
• End-stage renal disease (i.e., on dialysis or dialysis has been recommended)
• Pregnancy or women of childbearing potential not willing/able to use medically acceptable forms of contraception during protocol treatment or for at least 6 months following treatment

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Condition: Prostate Cancer, Metastatic Prostate Cancer, Androgen-independent Prostate Cancer, Recurrent Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02049190

Sponsor: Arno Therapeutics

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• 1. Male patients, 18 years of age or greater; 2. Histologically confirmed adenocarcinoma of the prostate (without neuroendocrine differentiation or small cell features); 3. In Stage 2, a mandatory biopsy is required with confirmed PR or APR in ≥1% tumor cells. For patients recruited to the abiraterone-onapristone combination arm, the biopsy must be performed on abiraterone administered as the most recent treatment and after a minimum of 2 weeks continuous treatment. For other patients, the biopsy must be taken at progression on or after abiraterone or enzalutamide or before screening with no anti-cancer treatment taken in the intervening period and a maximum of six (6) months prior to study start. If archival tissue is also available this should be provided for comparison purposes; a paired biopsy at day 8-28 is optional; 4. Metastatic or recurrent inoperable disease after previous surgery, radiation therapy, and/or chemotherapy; 5. For patients in Stage 1 and for patients in Stage 2 who will receive combination therapy with onapristone and abiraterone: no more than one prior chemotherapy regimen for CRPC (docetaxel rechallenge will be regarded as one line of chemotherapy); for patients in Stage 2 who will receive onapristone monotherapy: no prior chemotherapy is allowed; 6. Disease that has progressed by PSA or radiologically, on abiraterone or enzalutamide. Disease progression for study entry is defined as one or both of:
• PSA progression defined by a minimum of two rising PSA levels with an interval of ≥1 week between each determination.
• Radiological progression per RECIST 1.1; 7. For patients recruited to the abiraterone-onapristone combination arm, progression on abiraterone as their last line of treatment is required after a prior response to abiraterone; 8. The PSA value at screening and baseline should be ≥ 2 µg/L (2 ng/mL); 9. For onapristone monotherapy, corticosteroid discontinuation >4 weeks or >2 weeks with normal adrenal function confirmed by an ACTH stimulation test. For the combination onapristone
• abiraterone arm, prednisolone 5mg BID and no other steroid regimen allowed for 2 weeks prior to treatment initiation; 10. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); • For patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial; 11. Serum testosterone level < 1.7 nmol/L (50 ng/dL); 12. Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks; 13. Evaluable disease per RECIST 1.1 [Eisenhauer 2009] or Prostate Cancer Clinical Trials Working Group 2 (PCWG2) [Scher 2008]; 14. ECOG performance status 0-2; 15. Life expectancy ≥ 3 months; 16. Willing and able to sign written informed consent per ICH-GCP, the local regulatory requirements, and local data protection laws prior to study-specific screening procedures.

Exclusion Criteria:

1. Serum creatinine >1.5 ULN;
2. On ECG a QTc(F) interval >480 msec or any clinically significant cardiac rhythm abnormalities;
3. Liver function tests documented within the screening period and/or at baseline:
4. Total bilirubin > ULN (except in patients diagnosed with Gilbert's disease);
5. Alkaline phosphatase > 2.5 x UNL, unless test for alkaline phosphatase isoenzymes is elevated only for bone isoenzyme;
6. ALT/AST > UNL or > 2.5 x UNL in case of liver metastases;
7. Absolute neutrophil count < 1,500/µL, platelet count < 100,000/µL, and hemoglobin < 5.6 mmol/L (9 g/dL) and no growth factors or blood transfusions within 7 days of these values;
8. Serum albumin < 25 g/L (2.5 g/dL);
9. Known positive virology/serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B (surface antigen), or hepatitis C (testing not required);
10. Chronic inflammatory liver condition. History or clinical evidence of any liver or biliary pathology including cirrhosis, infectious disease, inflammatory conditions, steatosis, or cholangitis (including ascending cholangitis, primary sclerosing cholangitis, obstruction, perforation, fistula of biliary tract, spasm of sphincter of Oddi, biliary cyst or biliary atresia;
11. Patients with any other prior malignancy are not allowed except for:
12. Adequately treated basal cell or squamous cell skin cancer;
13. Adequately treated Stage I or II cancer from which the patient is currently in complete remission;
14. Other cancer from which the patient has been disease-free for 2 years;
15. For Stage 1 only: Chronic adrenal failure or is receiving concurrent long-term corticosteroid therapy. Prior long-term corticosteroids must be stopped ≥4 weeks or >2 weeks if normal adrenal function is confirmed by an ACTH stimulation test prior to start of study drug;
16. History or clinical evidence of any surgical or medical condition which the investigator judges as likely to interfere with the results of the study or pose an additional risk in participating; e.g., active or clinically significant history of disease involving a major organ system—vascular, cardiac, uncontrolled hypertension, pulmonary, gastrointestinal, hematologic, neurologic, neoplastic, renal, endocrine or immunodeficiency, or clinically significant active psychiatric disorders;
17. Used any prescription medication during the prior 2 weeks that the investigator judges is likely to interfere with the study or to pose an additional risk to the patient in participating, specifically inhibitors or inducers of cytochrome P450 (CYP)3A4 (see Appendix 4);
18. Received an investigational product or been treated with an investigational device within 30 days prior to first drug administration, or plans to start any other investigational product or device study within 30 days after last drug administration;
19. Received prior therapies within the following time period prior to receipt of first dose of study drug (Day 1, without withdrawal response and with no plans to initiate any of these during study:
20. Ketoconazole or bicalutamide within 6 weeks;
21. Systemic hormone therapy, chemotherapy, targeted therapies, antibodies within 4 weeks excluding abiraterone in the abiraterone-onapristone combination arm;
22. Fractionated radiotherapy within 3 weeks;
23. Single fraction of radiotherapy within 2 weeks;
24. Radionuclide therapy within 8 weeks;
25. Brachytherapy Pd-103 implant within the last 3 months;
26. Brachytherapy I-125 implants within 12 months.
27. Concurrent use of herbal products that may decrease PSA levels (e.g., saw palmetto);
28. Residual toxicity of prior anticancer treatment > grade 1 except for alopecia;
29. Brain metastases, active epidural disease or spinal cord compression, unless treated at least 4 weeks before entry, and stable with steroid treatment for ≥1 week;
30. Paget's disease of the bone;
31. Structurally unstable bone lesions suggesting impending fracture;
32. Patients with reproductive potential not employing adequate contraception during treatment and for 1 month after completing treatment;
33. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to swallow pills;
34. Mental incapacity or language barriers precluding adequate understanding, co-operation, and compliance with the study requirements;
35. Is, in the judgment of the investigator, unable or unwilling to comply with the requirements of the study.

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Condition: Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer AJCC v7, Metastatic Malignant Neoplasm in the Bone

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02565901

Sponsor: University of Washington

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
• Histologically or cytologically confirmed carcinoma of the prostate (excluding neuroendocrine differentiation or squamous cell histology)
• Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
• Castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and at least one of the following:
• PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
• Evaluable disease progression by modified RECIST 1.1
• Progression of metastatic bone disease on bone scan with > 2 new lesions
• Prior therapy with abiraterone, enzalutamide and/or docetaxel; if a patient has not received docetaxel or cabazitaxel chemotherapy, the patient must be informed of this treatment choice as an alternative; if the patient has received docetaxel or cabazitaxel chemotherapy or refuses one of both of these therapies, this rationale must be documented and the patient is then eligible; patient must be offered and made aware of all Food and Drug Administration (FDA)‐approved treatment options; patients with bone only disease may not have received radium-223
• The presence of metastatic disease amenable to computed tomography (CT) or ultrasound guided biopsy; this may include thoracolumbar vertebral bodies, pelvis, femur or humerus or soft tissue or nodal metastasis amenable to biopsy (excluding lung or pleural lesions)
• Agree to participate in biopsy of metastatic lesion during the study at day 21
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
• Life expectancy >= 12 weeks
• No prior malignancy is allowed except:
• Adequately treated basal cell or squamous cell skin cancer or
• In situ carcinoma of any site or
• Other adequately treated malignancy for which the patient is currently disease free for at least one year
• Patients with any prior chemotherapy regimens are eligible
• Patients with disease only in the bone may not have received Xofigo/radium 223 to avoid ongoing DNA damage in bone marrow
• Patients who are or are not receiving bisphosphonates or denosumab are eligible; bisphosphonates or denosumab should not be initiated after registration and during active treatment
• Absolute neutrophil count >= 1.5 x 10^9 cells/L (within 14 days prior to registration)
• Hemoglobin (Hgb) >= 9.0 g/dL (within 14 days prior to registration)
• Platelets >= 100,000 x 10^9/L (within 14 days prior to registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)
• Total bilirubin =< 1.5 x ULN (within 14 days prior to registration)
• Serum creatinine < 1.5 X institutional ULN mg/dL OR estimated glomerular filtration rate (eGFR) >= 50 mL/min (within 14 days prior to registration)

Exclusion Criteria:

• Patients currently receiving active therapy for other neoplastic disorders
• Patients with histologic evidence of small cell carcinoma of the prostate will not be eligible
• Patients with disease only in the bone previously treated with radium-223 will not be eligible
• Known parenchymal brain metastasis
• Active or symptomatic viral hepatitis or chronic liver disease
• Estimated creatinine clearance less than 50 ml/minute
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class II-IV heart disease
• Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy
• Administration of an investigational therapeutic within 30 days of cycle 1, day -2
• Patients with dementia/psychiatric illness/social situations that would limit compliance with study requirements or would prohibit the understanding and/or giving of informed consent
• Patients with medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained will not be eligible
• Any condition which, in the opinion of the investigator, would preclude participation in this trial
• Patients on anticoagulation therapy which cannot be held for metastatic biopsies

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04662580

Sponsor: Ambrx, Inc.

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Key Inclusion Criteria:

• Male subjects ≥ 18 years at the first time of providing written informed consent.
• Histologically confirmed prostate adenocarcinoma.
• Documented metastatic disease and evidence of disease progression
• Castration-resistant prostate cancer defined as surgical or medical castration with serum testosterone levels of ≤ 50 ng/dL (1.73 nM) at Screening. For patients who have not undergone an orchiectomy, must be undergoing treatment with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist and must agree to continue such therapy while on study treatment.
• Prior receipt of the following for metastatic prostate cancer:
• at least two lines of treatment
• at least two Food and Drug Administration (FDA)-approved therapies with at least one being a second-generation androgen receptor signaling inhibitor (e.g., abiraterone, darolutamide, apalutamide, or enzalutamide).
• Adequate blood counts

Key Exclusion Criteria:

• Use of chronic systemic glucocorticoids equivalent to > 10 mg prednisone daily. Note: short-term administration of systemic corticosteroids > 10 mg prednisone equivalent (e.g., for allergic reactions or management of immune- or infusion-related AEs) is allowed.
• Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, untreated CNS metastases are eligible provided they have been clinically stable (neurologically stable and not requiring steroids for at least 28 days prior to enrollment).
• History of any invasive malignancy (other than primary) within the previous 2 years prior to the enrollment date that requires active therapy or is at high risk of recurrence in the opinion of the investigator.
• Marked baseline prolongation of QT/QT interval corrected for heart rate (QTc), e.g., a triplicate-average QTc interval > 480 milliseconds (CTCAE Grade 2) using Fridericia's QT correction formula at any time within 28 days before enrollment, ongoing history of CTCAE Grade ≥2 QTc at enrollment, or anticipated need to perform repeat ECG evaluations to satisfy re-treatment criteria.
• Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease within 12 months prior to enrollment date,
• Clinically significant ocular findings by a qualified ophthalmologist or optometrist including active ocular infections or chronic corneal disorders unless approved by the Medical Monitor.
• Peripheral neuropathy Grade ≥ 2 within 28 days prior to enrollment.

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Condition: Metastatic Castration-Resistant Prostate Adenocarcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04077021

Sponsor: Calibr, a division of Scripps Research

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Men ≥ 18 years of age at time of informed consent
• For Part 1 and Part 2: men with metastatic castration resistant prostate cancer (mCRPC) with histologically or cytologically confirmed adenocarcinoma of the prostate as defined by one or more of the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria
• Patients with treated brain metastasis or LMD are eligible if brain imaging shows no evidence of progression
• Must have prostate-specific antigen (PSA) and/or radiographic progression on AT LEAST One novel androgen receptor (AR)-targeted therapy (abiraterone acetate, enzalutamide).
• Eastern Cooperative Oncology Group performance status of 0-1
• Adequate liver function
• Adequate hematopoietic function
• Testosterone level ≤ 50 ng/mL (or 1.73 nmol/L)
• Patient has a life expectancy of greater than 12 weeks

Exclusion Criteria:

• Patients whose tumors solely exhibit neuroendocrine differentiation or small cell features by histopathology
• Patients with new or progressive brain metastasis or Leptomeningeal Disease (LMD)
• Patients with a history of clinically significant cardiovascular disease such as symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, history of stroke or myocardial infarction within 6 months of enrollment
• Patients with peripheral neuropathy CTCAE Grade >/= 2
• Patients with a known history of hypersensitivity, allergy or intolerance to CCW702 or its excipients
• Patients with untreated or imminent spinal cord compression

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04421222

Sponsor: ESSA Pharmaceuticals

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Male 18 years of age or older.
• Histologically, pathologically, or cytologically confirmed prostate cancer without small cell features.
• Evidence of castration-resistant prostate cancer (CRPC).
• Presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
• Limited further treatment options available known to confer clinical benefit in this disease setting from the perspective of the treating physician. Specifically, patients must have progressed on at least 2, but not more than 3, prior approved systemic therapies for mCRPC which include at least one, but not more than 2, second generation anti-androgen drug.
• Patients may have received prior docetaxel for mCSPC or mCRPC but must not have had disease progression during, or within 6 months of completing chemotherapy. Only one line of prior chemotherapy is allowed.
• Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria.
• The patient must have recovered from toxicities related to any prior treatments.
• Castrate at screening.
• Patients receiving bisphosphonates or other approved bone-targeting therapy must be on a stable dose for at least 4 weeks prior to the start of study drug.
• Demonstrate adequate organ function.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. Part A/Phase 1b (Dose Expansion) Inclusion Criteria: The inclusion criteria for this cohort are the same as for Phase 1a with the exception of: limit of prior therapies to 2 and prior chemotherapy is not allowed for this cohort of patients. Part B/Cohort 1 (EPI-7386 in combination with AAP) Inclusion Criteria:
• Patients are eligible to enroll in this cohort if they meet the clinical criteria for receiving AAP as standard of care treatment as per label (i.e., high-risk mHSPC or mCRPC).
• All other inclusion criteria listed for Part A/Phase 1a apply except for those that do not apply to mHSPC or mCRPC patients (i.e. evidence of CRPC and limited treatment options for mCRPC). Part B/Cohort 2 (Window of Opportunity with clinical endpoints followed by combination with Apalutamide)
• Male 18 years of age or older.
• Histologically, pathologically, or cytologically confirmed prostate cancer without small cell features.
• Evidence of castration-resistant prostate cancer (CRPC).
• Patients who received a first generation anti-androgen as part of an initial combined androgen blockade therapy or as second-line hormonal therapy must show continuing disease (PSA) progression off the anti-androgen for at least 4 weeks prior to enrollment.
• At least 4 weeks must have elapsed from the use of 5-α reductase inhibitors, estrogens, and any other anti-cancer therapy prior to enrollment.
• At least 4 weeks must have elapsed from major surgery or radiation therapy prior to enrollment.
• The patient must have recovered from toxicities related to any prior treatments.
• Castrate at screening.
• Demonstrate adequate organ function.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. Part A Phase 1a and Phase 1b Exclusion Criteria:
• Biologic anti-cancer therapy or a cytotoxic chemotherapy within 4 weeks prior to the start of study drug.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 4 weeks prior to the start of study drug.
• Any lutamides or abiraterone within 14 days or 5 half-lives, whichever is longer prior to start of study drug.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study drug.
• Received limited-field palliative bone radiotherapy >5 fractions and/or any radiotherapy within 2 weeks prior to the start of study drug.
• Received a blood transfusion within 28 days of screening.
• Received prior chemotherapy (for Part 1b Cohort A only).
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 4 weeks before enrollment.
• Spinal cord compression.
• Diagnosis of another invasive malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma.
• Gastrointestinal disorder affecting absorption.
• Significant cardiovascular disease.
• Concurrent disease or any clinically significant abnormality.
• Use of strong inducers of CYP3A within 14 days of the first dose of study drug. Part A Phase 1b (Dose Expansion) Exclusion Criteria: The exclusion criteria for this cohort are the same as the criteria from Phase 1a with the addition of the following: • Any prior treatment with chemotherapy. Part B Cohort 1 (EPI-7386 in combination with AAP) Exclusion Criteria: The

Exclusion Criteria:

• Biologic anti-cancer therapy or a cytotoxic chemotherapy within 4 weeks prior to the start of study drug.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 4 weeks prior to the start of study drug.
• Any lutamides or abiraterone within 14 days or 5 half-lives, whichever is longer prior to start of study drug.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study drug.
• Received limited-field palliative bone radiotherapy >5 fractions and/or any radiotherapy within 2 weeks prior to the start of study drug.
• Received a blood transfusion within 28 days of screening.
• Received prior chemotherapy (for Part 1b Cohort A only).
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 4 weeks before enrollment.
• Spinal cord compression.
• Diagnosis of another invasive malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma.
• Gastrointestinal disorder affecting absorption.
• Significant cardiovascular disease.
• Concurrent disease or any clinically significant abnormality.
• Use of strong inducers of CYP3A within 14 days of the first dose of study drug. Part A Phase 1b (Dose Expansion) Exclusion Criteria: The exclusion criteria for this cohort are the same as the criteria from Phase 1a with the addition of the following: • Any prior treatment with chemotherapy. Part B Cohort 1 (EPI-7386 in combination with AAP) Exclusion Criteria: The exclusion criteria for this cohort are the same as the criteria from Phase 1a with the addition of the following:
• Use of concomitant CYP2D6 substrates with narrow therapeutic index.
• Known allergies, hypersensitivity, or intolerance to the excipients of AA (refer to AA Investigator's Brochure [IB] or package inserts as appropriate). Part B Cohort 2 (Window of Opportunity with clinical endpoints followed by combination with Apalutamide)
• Presence of distant metastases, including visceral, nodal and bones involvement. Exception: pelvic lymph nodes < 2 cm in short axis (N1) located below the iliac bifurcation are allowed.
• Symptomatic loco-regional disease requiring medical intervention, such as moderate or severe urinary obstruction or hydronephrosis due to primary tumor.
• Prior treatment with second generation anti-androgens.
• Prior treatment with CYP17 inhibitors.
• Prior treatment with radiopharmaceutical agents, immunotherapy, or any other investigational agent for nmCRPC.
• Prior chemotherapy.
• History or evidence of: prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 3 years prior to enrollment; severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events; uncontrolled hypertension.
• Gastrointestinal disorder affecting absorption.
• Use of strong inducers of CYP3A within 14 days of the first dose of study drug.

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Condition: Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, Castration Resistant Prostatic Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05519449

Sponsor: Janux Therapeutics

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum 100 Years
• Gender: Male

Inclusion Criteria:

• Male ≥18 years of age at the time of signing informed consent
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Having mCRPC that progressed after at least one novel anti-androgen therapy and at least one taxane containing regimen. Participants who have actively refused a taxane containing regimen or are medically unsuitable to receive taxane are eligible
• Adequate organ function

Exclusion Criteria:

• Prior solid organ transplant
• Prior treatment with PSMA-targeted CAR-T cell therapy or PSMA-CD3, PSMA-CD28 or other CD3 T-cell engaging bispecific antibodies
• Clinically significant cardiovascular disease
• Active clinically significant infection (bacterial, viral, fungal, mycobacteria or other)
• Any medical condition or clinical laboratory abnormality likely to interfere with assessment of safety or efficacy of study treatment

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Condition: Metastatic Castration Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02566772

Sponsor: Taiho Oncology, Inc.

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. Male ≥18 years of age
2. Histological or cytological evidence of metastatic castrate resistant prostate cancer (excluding neuroendocrine differentiation and small cell histology) who are castration resistant and have:
3. Dose escalation: documented progression defined in PCWG3 and/or intolerance to abiraterone and/or enzalutamide therapy, as well as 1 or more chemotherapies.
4. Expansion: I. Group A: documented progression after abiraterone or enzalutamide and chemotherapy consisting of no more than 2 prior taxane-based therapies ii. Group B: documented progression after only abiraterone or enzalutamide therapy without any chemotherapy iii. Measurable disease per RECIST 1.1 and/or bone metastases
5. ECOG performance status of ≤1 on Day 1 Cycle 1
6. Ongoing androgen deprivation with serum testosterone <50 ng/dL
7. Expansion Phase only: willingness to undergo baseline core biopsies, if feasible
8. Ability to take medication orally
9. Adequate organ function
10. Agree to use effective contraception during the study and for 30 days after the last dose of TAS3681
11. Willing to comply with scheduled visits and procedures

Exclusion Criteria:

1. QTcF ≥ 450 ms, history of QTc prolongation or predisposition for QTc prolongation or family history of sudden cardiac death or QT prolongation
2. History or presence of heart failure or left ventricular dysfunction with ejection fraction <40% within the previous 6 months; if >6 months cardiac function within normal limits and free of cardiac-related symptoms
3. History or presence of atrial fibrillation, atrial flutter, or paroxysmal supraventricular tachycardia; the presence or history of ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia
4. Presence of cardiac pacemaker or implantable cardioverter-defibrillator
5. History or presence of bradycardia or conduction abnormalities
6. History or presence of cardiac arrest or unexplained syncope
7. Hypokalemia
8. History of myocardial infarction or severe unstable angina
9. Any medication administered within 2 weeks prior to 1st dose of TAS3681 that is known to prolong the QT interval or be arrhythmogenic
10. Received G-CSF, radiotherapy for extended field, anticancer chemotherapy, investigational agents, or major surgery within 4 weeks of study drug administration; receipt of anticoagulant or CYP3A inhibitor within 2 weeks of study drug administration
11. Serious illness or medical condition that could affect the safety or tolerability of study treatments
12. Received prior treatment with TAS3681
13. User of herbal products
14. Any condition or reason that in the opinion of the investigator, interferes with the ability of the participant to participate in the trial
15. To be eligible to participate in the food effect assessment (Escalation Phase only), participants must not have a history or presence of any clinically significant abnormality involving the gastrointestinal tract and an inability to fast for a minimum of 8 hours

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Condition: Advanced Solid Tumor, Castration-Resistant Prostatic Cancer, Malignant Melanoma, Pancreatic Ductal Carcinoma, Hepatocellular Cancer, Epithelial Ovarian Cancer, Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05293496

Sponsor: MacroGenics

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• 1. Ability to provide and document informed consent and willing and able to comply with all study procedures.
• Participants diagnosed with advanced solid tumors including but not limited to metastatic castration-resistant prostate cancer, melanoma, pancreatic cancer, hepatocellular carcinoma, ovarian cancer and renal cell carcinoma.
• Participants have received approved therapies according to their diagnosis.
• Participants must have an available tumor tissue sample. A fresh tumor biopsy may be performed if no archival sample is available.
• Eastern Cooperative Oncology Group performance status of less than or equal to 2.
• Life expectancy of at least 12 weeks.
• Evidence of measurable tumor for evaluation
• Acceptable end organ function according to laboratory results.
• Patients must agree to use highly-effective contraception during the study, and not donate sperm or ova.

Exclusion Criteria:

• Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
• Another malignancy that required treatment within the past 2 years. Participants who have had curative therapy for non-melanomatous skin cancer, localized prostate cancer (Gleason score < 6), or carcinoma in situ are eligible for the study.
• Active viral, bacterial, or fungal infection requiring systemic treatment within 1 week of initiation of study drug. Participants are eligible after SARS CoV 2-related symptoms have fully recovered for ≥ 72 hours.
• History of immunodeficiency. Participants with HIV are eligible if they have a CD4+ count ≥ 300/µL, undetectable viral load, and maintained on antiretroviral therapy for a minimum of 4 weeks.
• Prior autologous/allogeneic stem cell or tissue/solid organ transplant
• Prior treatment with MGD009, enoblituzumab, or other B7-H3 targeted agents for cancer.
• Clinically significant cardiovascular disease, lung compromise, venous insufficiency, or gastrointestinal disorders.
• Participants with greater than Grade 1 peripheral neuropathy.
• Participants who have a history of severe adverse events (AEs) from immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, or CTLA-4 inhibitors). All other AEs from prior immune checkpoint inhibitors must be resolved to Grade 1 or less. Participants with any grade neurologic toxicity from prior immune checkpoint inhibitors are excluded.
• Pleural effusion or ascites. Trace pleural or peritoneal fluid is not exclusionary.
• History of Guillain-Barre syndrome, myasthenia gravis, or other autoimmune sensory or motor neuropathies.

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Condition: Castration-Resistant Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03317392

Sponsor: National Cancer Institute (NCI)

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Participants must be male aged >= 18 years of age
• Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate
• Participants must have castrate levels of serum testosterone < 50 ng/dL
• Participants without orchiectomy must be maintained on luteinizing hormone releasing hormone (LHRH) agonist/antagonist; participants receiving prior docetaxel abiraterone, or next generation AR antagonist (enzalutamide, apalutamide, or darolutamide) for hormone sensitive disease are permitted
• Participants must have progressive disease as defined by any of the following:
• Castrate resistant disease as defined by PCWG-3 criteria; participants must have a rise in PSA on two successive determination at least one week apart and PSA levels >= 2 ng/mL (only the screening PS needs to be >= 2 ng/mL) and serum testosterone < 50 ng/dL
• Soft tissue progression as defined by RECIST version 1.1
• Bone disease progression as defined by PCWG-3 criteria including the development of two or more new lesions on bone scan
• Participants must have >= 2 bone metastases by radiographic imaging and at least 1 lesion which has not been treated with prior radiation therapy
• Participants must have tumor accessible for biopsy and be agreeable to baseline tumor biopsy; a metastatic focus is preferred but if not available and prostate is still intact prostate biopsy can be performed
• Availability at the study site of formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens, when available
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)
• White blood cell count (WBC) >= 3,000/mcL (within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days prior to administration of study treatment)
• Platelets >= 100,000/mcL (within 28 days prior to administration of study treatment)
• Hemoglobin >= 10 g/dL (transfusions permitted) (within 28 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment); for subjects with Gilbert's disease =< 3.0 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to administration of study treatment)
• Creatinine clearance >= 51 ml/min as defined by Cockcroft-Gault equation (within 28 days prior to administration of study treatment)
• Participants should be receiving an osteoclast targeting agent including either bisphosphonates or denosumab except in patients with contraindications as determined by the treating investigator including:
• Hypocalcemia
• Hypophosphatemia
• Renal impairment including those with a glomerular filtration rate < 35 mL/min using the Cockcroft-Gault equation
• Hypersensitivity to drug formulation
• Dental condition or need for dental intervention that per the investigator would increase the risk of osteonecrosis of the jaw
• The effects of olaparib and radium-223 on the developing human fetus are unknown; for this reason, men treated or enrolled on this protocol must agree to use adequate contraception and avoid sperm donation prior to the study, for the duration of study participation, and three months after discontinuation of olaparib and radium-223 administration
• Human immunodeficiency virus (HIV)-positive with negative viral loads on stable antiretroviral regimen and CD4 count > 250 are eligible
• Ability to understand and the willingness to sign a written informed consent document; patients with impaired decision-making who have a legal guardian (e.g., spouse) able to make informed decisions on behalf of the patient are eligible
• Patients must be able to tolerate oral medications by mouth and not have a gastrointestinal illness that would preclude absorption of olaparib

Exclusion Criteria:

• Pathology consistent with small cell carcinoma of the prostate
• Presence of visceral metastases (liver, lung, brain, etc.) or malignant lymphadenopathy exceeding 4 centimeters (cm) in short diameter
• Prior treatment with radium-223
• Prior treatment with olaparib or other PARPi
• Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation; treatment with cytotoxic chemotherapy within 3 weeks of treatment initiation; treatment with investigational prostate cancer directed therapy within 4 weeks of treatment initiation; treatment with enzalutamide within 4 weeks of treatment initiation
• Prior hemibody external radiotherapy
• Palliative radiation therapy to the bone or other sites within 2 weeks of treatment initiation
• Participants who are receiving any other investigational agents
• Imminent or established spinal cord compression based on clinical and/or imaging findings
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring need for intravenous anti-microbials, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Clinically significant medical condition defined as:
• Cerebral infarction within 6 months of study treatment
• Transient ischemic attack within 3 months of study treatment
• Myocardial infarction within 6 months of study treatment
• Uncontrolled angina within 3 months of study treatment
• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan performed within 3 months of the screening visit results in a left ventricular ejection fraction that is >= 45%
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)
• Prolonged corrected QT interval by the Fridericia correction formula on the screening electrocardiogram (ECG) > 470 msec (as determined on 2 or more time points within a 24 hour period if the first ECG demonstrates a prolonged corrected QT interval) or family history of long QT syndrome
• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
• Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
• History of hypertensive emergency or encephalopathy within 6 months of study treatment
• Deep venous thrombosis or pulmonary embolism within 3 months of study treatment
• Major surgery within 4 weeks of study treatment; subjects with clinically relevant ongoing complications from prior surgery are not eligible
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
• Patient unable to swallow orally administered medication
• History of bowel obstruction within 1 month of study treatment
• History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation within the 3 months of study treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib or radium-223
• Participants receiving strong CYP3A4/5 inducers or inhibitors are ineligible; dihydropyridine calcium-channel blockers are permitted for management of hypertension; the required washout period prior to starting olaparib is 2 weeks for CYP3A inhibitors; the required washout period prior to starting olaparib is 4 weeks for enzalutamide or phenobarbital and 3 weeks for other CYP3A inducers
• Patients with known active hepatitis (i.e. hepatitis B or C) infection
• Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML
• Patient having received prior allogenic bone marrow transplant or double umbilical cord blood transplantation
• Individuals with a history of a different malignancy are ineligible except for the following circumstances:
• Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or
• Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: superficial bladder cancer, basal cell or squamous cell carcinoma of the skin

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05075577

Sponsor: ESSA Pharmaceuticals

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Males ≥18 years.
• Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma.
• Evidence of castration-resistant prostate cancer (CRPC).
• Presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
• Naïve to second generation anti-androgens.
• Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy or history of bilateral orchiectomy, with castrate level testosterone.
• Serum testosterone ≤1.73 nmol/L (50 ng/dL).
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days prior to the start of study treatment.
• Demonstrate adequate organ function.

Exclusion Criteria:

• Biologic anti-cancer therapy within 28 days prior to the start of study treatment.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days prior to the start of study treatment.
• Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 28 days prior to the start of study treatment or plans to initiate during the study.
• Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs within 28 days of the first dose of study treatment.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study treatment.
• Received limited-field palliative bone radiotherapy >5 fractions and/or any radiotherapy within 2 weeks prior to the start of study treatment.
• Received a blood transfusion within 28 days of hematologic screening labs.
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 28 days before signing of informed consent.
• Spinal cord compression.
• Diagnosis of another clinically significant malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma and other in situ or non-invasive malignancies.
• Gastrointestinal issues affecting absorption.
• Significant cardiovascular disease.
• Known history of seizure or conditions that may pre-dispose them to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation.
• Concurrent disease or any clinically significant abnormality.
• Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide.
• Use of strong inhibitors of CYP2C8.
• Use of strong inducers of CYP3A.
• Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and CYP2B6.
• Use of granulocyte colony stimulating factor within 7 days prior to screening laboratories.
• Not a candidate for enzalutamide treatment.
• Patients with rare hereditary problems of fructose intolerance.

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Condition: Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05917470

Sponsor: Oncternal Therapeutics, Inc

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Subject is ≥18 years of age
• Subject has histologically documented metastatic adenocarcinoma of the prostate confirmed by biopsy without neuroendocrine differentiation or small cell features.
• Subjects has a history of metastatic CRPC.
• Subject has R/R disease following treatment with at least one next-generation AR-signaling inhibitor.
• Subject has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or evaluable bony disease. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• Subject has an Eastern Cooperative Oncology Group performance status of 0,1 or 2, and life expectancy of ≥ 6 months.
• Subject agrees to take or continue luteinizing hormone-releasing hormone agonist or antagonist therapy or has undergone bilateral orchiectomy.
• At least 2 weeks or five half-lives have elapsed, whichever is earliest, since last systemic therapy, including taxanes or other chemotherapy. At least one month has elapsed since systemic therapy with radionuclide pharmaceutical agents
• Subject has evidence of disease progression on or after their most recent systemic treatment
• Subject has a PSA level ≥ 10 ng/mL, or ≥ 2 ng/mL and ≥ 50% increase from nadir on prior therapy, whichever is lowest.
• Subject has serum testosterone < 50 ng/dL.
• Subject has adequate renal, hepatic, and pulmonary function
• Subject is committed to practice true abstinence, or use a highly effective method of contraception with any female partner of childbearing potential unless documented to be surgically sterile (i.e., vasectomy or bilateral orchiectomy) and to not make semen donations during the study and for 3 months after the last dose of study drug.

Exclusion Criteria:

• Subject has small cell prostate cancer or neuroendocrine disease histology, including mixed histology.
• Subject has metastases to the brain or central nervous system
• Subject is receiving concurrent anti-cancer therapy (including chemotherapy, antibody therapy, immunotherapy, cellular therapy, or other experimental therapies) except for ongoing androgen inhibiting therapy such as luteinizing hormone-releasing hormone (LHRH) agonists. Supportive non-cancer directed therapies such as bisphosphonates or denosumab are allowed.
• Subjects taking a strong inhibitor of CYP3A4 or a substrate of CYP2C9 or CYP2C19
• Subject had major surgery within 30 days prior to start of study drug.
• Subject has current, untreated pathologic long-bone fractures(s), or risk of imminent pathologic fracture(s).
• Subject has current or imminent spinal cord compression.
• Subject has an active seizure disorder or a history of seizure disorder(s).
• Subject has evidence of active human immunodeficiency virus infection, hepatitis B virus (HBV), or hepatitis C virus (HCV)
• Subject has any other serious illness or medical condition that would interfere with study participation
• Subject has abnormal electrocardiograms (ECGs) that are clinically significant, including average QTcF > 450 ms, or a history of Torsade de Pointes.
• Subject has any infection requiring parenteral antibiotic therapy or causing fever (temperature >100.5°F or 38.1°C) within 1 week prior to first dose.
• Clinically significant other malignancy with the potential to confound study assessments, with the exception of e.g., treated cutaneous squamous cell and basal carcinomas, non-muscle invasive bladder cancer, Rai Stage 0 CLL, and adequately treated Stage 1 to 2 non-cutaneous malignancy in remission for 5 years.
• Subject is unable to comply with the protocol and/or not willing or not available for follow-up assessments
• Subject has any medical intervention or other condition which, in the opinion of the Investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives.

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Condition: Metastatic Castration-resistant Prostate Cancer (mCRPC), Clear Cell Renal Cell Carcinoma (ccRCC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03972657

Sponsor: Regeneron Pharmaceuticals

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Key Inclusion Criteria:

1. mCRPC cohorts:
2. Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma.
3. Prostate specific antigen (PSA) value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol.
4. Has received ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to androgen deprivation therapy [ADT]) including at least:
5. one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)
6. post-177Lu-PSMA-617 radiotherapy expansion cohort only. Must have received at least 2 doses of 177Lu-PSMA-6
7. ccRCC cohorts:
8. Men and women with histologically or cytologically confirmed RCC with a clear-cell component.
9. Diagnosis of metastatic ccRCC with at least one measurable lesion via RECIST 1.1 criteria
10. Has progressed on or after ≥1 line prior systemic therapy approved in the metastatic setting. Prior treatment must include an anti-programmed death-1 (receptor) [PD-1]/programmed death-ligand 1 (PD-L1) therapy and either ipilimumab and/or a tyrosine kinase inhibitor

Key Exclusion Criteria:

1. Has received treatment with an approved systemic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities, as described in the protocol
2. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy, as described in the protocol
3. Has received prior PSMA-targeting therapy with the exception of approved radiopharmaceutical therapy (eg. 177Lu-PSMA-617) in mCRPC patients
4. Dose Escalation: Has had prior anti-cancer immunotherapy (other than sipuleucel-T) within 5 half-lives prior to study therapy.
5. Dose Expansion (mCRPC only): Has had prior anti-cancer immunotherapy, as describe in the protocol
6. Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study therapy
7. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
8. Encephalitis, meningitis, neurodegenerative disease (with the exception of mild dementia that does not interfere with activities of daily living [ADLs]) or uncontrolled seizures in the year prior to first dose of study therapy
9. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency NOTE: Other protocol defined Inclusion/

Exclusion Criteria:

1. apply

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Condition: Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02826772

Sponsor: Suzhou Kintor Pharmaceutical Inc,

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• 1. Written informed consent obtained prior to any study-related procedure being performed. 2. Subjects at least 18 years of age or older at the time of consent. 3. Histologically confirmed metastatic castrate resistant cancer (mCRPC) who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel, for example); or cannot tolerate either or both of these classes of therapies. 4. Ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) "super-agonist" or antagonist, or bilateral orchiectomy and serum testosterone level < 50 ng/dL (< 0.5 ng/mL, < 1.7 nmol/L) at screening. 5. Metastatic disease documented by computed tomography (CT)/magnetic resonance imaging (MRI) or bone scan. 6. Progressive disease despite ongoing androgen deprivation or chemotherapy. Progressive disease is defined by 1 or more of the following criteria:
• Subjects with a rising PSA value > 2 ng/mL in at least 2 measurements, at least 1 week apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for the rising PSA is required to document progression.
• Subjects with measurable disease, progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Subjects with metastatic bone disease, progression defined by 2 or more new lesions in a radionuclide bone scan. 7. ECOG performance status of 0-2 (dose escalation phase); ECOG performance status of 0-1 (expansion phase). 8. Screening blood counts of the following:
• Absolute neutrophil count ≥ 1500/μL
• Platelets ≥ 100,000/μL
• Hemoglobin > 9 g/dL 9. Screening chemistry values of the following:
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 × upper limit of the normal reference range (ULN)
• Total bilirubin ≤ 2 × ULN
• Creatinine ≤ 1.5 × ULN
• Albumin > 2.8 g/dL. 10. At screening, life expectancy of at least 3 months. 11. Subjects whose partners are women of childbearing potential (WOCBP) must use an adequate method of birth control while on study drug and at least for 3 weeks after discontinuation of study drug. 12. Subject is willing and able to comply with all protocol required visits and assessments.

Exclusion Criteria:

1. Subjects with life expectancy less than 3 months.
2. Discontinuation of bicalutamide or nilutamide less than 6 weeks, and other antiandrogens less than 4 weeks, abiraterone less than 3 weeks, prior to the start of study medication.
3. Prior chemotherapy, radiation, sipuleucel-T or other experimental immunotherapy less than 4 weeks prior to the start of study medication.
4. Prior chemotherapies more than 2 lines (Phase II part only) .
5. Ongoing acute treatment-related toxicity associated with a previous therapy greater than grade 1 except for grade 2 alopecia or neuropathy.
6. History of impaired adrenal gland function (eg, Addison's disease, Cushing's syndrome).
7. Known gastrointestinal disease or condition that affects the absorption of GT09
8. History of congestive heart failure New York Heart Association (NYHA) class III or IV or uncontrolled hypertension at screening.
9. History or family history of long QT syndrome.
10. History of other malignancy within the previous 3 years, except basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer.
11. Use of systemic glucocorticoid (eg, prednisone, dexamethasone) within 14 days prior to the start of study medication.
12. Co-administration of CYP3A4 ligands that serve as substrates or induce or inhibit the enzyme.
13. Prior use of any herbal products known to decrease PSA levels (eg, PC-SPES or saw palmetto) within 30 days prior to the start of study medication.
14. Major surgery within 30 days prior to the start of study medication.
15. Blood transfusion (including blood products) within 1 week of screening.
16. Serious persistent infection within 14 days prior to the start of study medication.
17. Serious concurrent medical condition including CNS disorders.
18. Previous history of difficulty swallowing capsules.
19. Known hypersensitivity to GT0918 or its excipients.
20. Any condition that, in the opinion of the investigator, would impair the subject's ability to comply with study procedures.

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Condition: Metastatic Castration Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04179396

Sponsor: Clovis Oncology, Inc.

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Have signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form prior to any study-specific evaluation
• Be ≥18 yrs of age at the time the informed consent form is signed
• Be either AR-directed therapy-naive or have received 1-2 lines of AR-directed therapy in the castration-resistant setting.
• Adequate organ function
• ECOG 0 or 1
• Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate that is metastatic
• Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)
• Have disease progression after initiation of most recent therapy

Exclusion Criteria:

• Active second malignancy, with the exception of curatively treated non melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
• Have received greater than 2 previous lines of chemotherapy for mCRPC
• Prior treatment with any PARP inhibitor
• Symptomatic and/or untreated central nervous system metastases
• Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of study drug
• Spinal cord compression, symptomatic and/or untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients with asymptomatic previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks
• Any clinically significant cardiovascular disease
• Taking any concomitant medications or herbs that could interfere or interact with the study drug

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Condition: Metastatic Castration Resistant Prostate Cancer (mCRPC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03480646

Sponsor: Constellation Pharmaceuticals

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Adults (Age ≥ 18 years)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy of at least 12 weeks
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Progressive disease in the setting of medical or surgical castration (i.e. CRPC)
• Documented metastatic disease
• Must have undergone bilateral orchiectomy (surgical castration) or be willing to continue gonadotropin-releasing hormone (GnRH) analog or antagonist (medical castration)
• Serum testosterone <50 ng/dL
• Receipt of prior line of second generation androgen inhibitor
• Demonstrate adequate organ function as defined below:
• Absolute Neutrophil Count (ANC) ≥ 1,000/μL
• Platelet Count ≥ 100,000/μL
• Hemoglobin (Hgb) ≥ 8 g/dL
• Serum creatinine ≤ 2 × upper limit of normal (ULN) OR
• Creatinine clearance (CrCl) ≥ 40 mL/min as estimated by the Cockcroft and Gault formula1 in subjects with creatinine > 2 X ULN
• Bilirubin ≤ 1.5 × ULN unless evidence of Gilbert's disease in which case < 3 x ULN
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN without liver metastases; must be ≤ 5 × ULN with liver metastases
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN without liver metastases; must be ≤ 5 × ULN with liver metastases

Exclusion Criteria:

• Known symptomatic brain metastases (NOTE: patients with treated epidural disease are allowed)
• Treatment with any of the following for prostate cancer within the indicated timeframe prior to day 1 of treatment: 1. First generation: AR antagonists (e.g., bicalutamide, nilutamide, flutamide) within 4 weeks 2. 5 alpha reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol [DES]), or progesterones within 2 weeks 3. Chemotherapy within 3 weeks 4. Biologic therapy within 4 weeks 5. Investigational therapy within 3 weeks (or within a time interval less than at least 5 half-lives of the investigational agent [if known], whichever is longer). 6. Immunotherapy within 4 weeks 7. Prior radionuclide therapy within 4 weeks

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Condition: Metastatic Castration-resistant Prostate Cancer, Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05011188

Sponsor: Rahul Aggarwal

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

1. Histologically confirmed metastatic prostate adenocarcinoma.
2. Disease progression by PCWG3 criteria at study entry.
3. Prior progression by PCWG3 criteria on one or more androgen signaling inhibitors including abiraterone acetate, enzalutamide, apalutamide, and/or darolutamide.
4. No prior taxane-based chemotherapy for the treatment of mCRPC. Prior taxane use in the castration-sensitive prostate cancer (CSPC) setting allowed provided last dose > 6 months prior to study entry.
5. Patients must be evaluable for the primary endpoint of composite response, and must have either serum PSA ≥ 2 ng/mL during Screening and/or measurable disease by RECIST 1.1 criteria.
6. Participants must be willing to undergo metastatic tumor biopsy during Screening. If there is no safely accessible metastatic lesion, this requirement will be waived.
7. Dose Expansion only: Participants must be willing to undergo CD46-directed Positron Emission Tomography (PET) imaging during Screening (Co-enrolling on NCT05245006, Groups B and C)
8. Castrate level of serum testosterone at study entry (<50 ng/dL). Patients without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study.
9. No other systemic anti-cancer therapies administered other than LHRH analogue within 14 days or, 5 half-lives, whichever is shorter, prior to initiation of study treatment. Adverse events related to prior anti-cancer treatment related to therapies other than LHRH analogue must have recovered to Grade ≤ 1 with the exception of any grade alopecia. a. Patients receiving enzalutamide prior to study entry may continue treatment at their current enzalutamide dose level without requirement for wash-out period.
10. Age >=18 years.
11. Eastern Cooperative Oncology Group (ECOG) performance status <= 1 (Karnofsky performance status >= 70 percent (%)).
12. Demonstrates adequate organ function as defined below:
13. Absolute neutrophil count ≥ 1,500/microliter (mcL).
14. Platelets >= 100,000/mcL and no platelet transfusions during the 14 days prior to first dose of FOR
15. Hemoglobin >= 8.0 grams per deciliter (g/dL) without red blood cell transfusion during the 14 days prior to first dose of FOR
16. Total bilirubin <=1.5 x institutional upper limit of normal (ULN), unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
17. Aspartate aminotransferase (AST) /serum glutamic-oxaloacetic transaminase (SGOT) <=3 x institutional institutional upper limit of normal (ULN).
18. Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) =3 x ULN.
19. Serum creatinine <= 1.5 x institutional upper limit of normal OR Calculated creatinine clearance glomerular filtration rate (GFR) >= 60 mL/min, calculated using the Cockcroft-Gault equation.
20. Serum sodium level >=130 mmol/L.
21. Ability to understand a written informed consent document, and the willingness to sign it.
22. Individuals with concurrent second malignancy requiring active treatment at study entry. Nonmelanoma skin cancer, non-muscle invasive bladder cancer, and other carcinomas-in-situ are allowable exceptions.
23. Patients must agree to use adequate contraception prior to the study, for the duration of study participation, and 60 days after last administration of study treatment. Adequate contraception includes:
24. Patients who are sexually active should consider their female partner to be of childbearing potential if she has experienced menarche and is not postmenopausal (defined as amenorrhea > 24 consecutive months) or has not undergone successful surgical sterilization. Even women who use contraceptive hormones (oral, implanted, or injected), an intrauterine device, or barrier methods (diaphragms, condoms, spermicide) should be considered to be of childbearing potential.
25. Acceptable methods of contraception include continuous total abstinence, or double-barrier method of birth control (e.g. condoms used with spermicide, or condoms used with oral contraceptives). Periodic abstinence and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

1. Has received prior radiotherapy within 2 weeks of first dose of FOR
2. Prior treatment with FOR46 or another CD46-targeting therapeutic agent.
3. Prior histologic evidence of de novo or treatment-emergent small cell neuroendocrine prostate cancer. Pathologic assessment of baseline tumor biopsy performed during Screening is not required for determination of study eligibility.
4. Cardiac condition as defined as one or more of the following:
5. Uncontrolled supraventricular arrhythmia or ventricular arrhythmia requiring treatment.
6. New York Heart Association (NYHA) congestive heart failure class III or IV.
7. History of unstable angina, myocardial infarction, or cerebrovascular accident within 6 months prior to Cycle 1, Day
8. History of seizure or pre-disposing condition including:
9. History of brain metastasis.
10. Cerebrovascular accident (CVA) within 6 months prior to study entry.
11. History of intracranial hemorrhage.
12. History of pneumonitis.
13. Is receiving systemic steroid therapy at a prednisone equivalent dose of > 10 milligram daily or other form of immunosuppressive therapy within 7 days prior to first dose of study drug.
14. Has an active infection requiring intravenous antibiotics within 7 days prior to Cycle 1, Day
15. Use of a prohibited concomitant medication within 7 days of first dose of FOR46, including: a. Strong inhibitor of CYP3A4 (boceprevir, clarithromycin, cobicistat, conivaptan, diltiazem, danoprevir/ritonavir, elvitegravir/ritonavir, grapefruit juice, idelalisib, indinavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, paritaprevir/ritonavir/ombitasvir and/or dasabuvir, posaconazole, ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, troleandomycin, and voriconazole).
16. Major surgery within 28 days prior to Cycle 1, Day
17. Minor procedures including biopsies, dental surgery, cataract surgery, or outpatient procedure are allowed.
18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02494921

Sponsor: Rahul Aggarwal

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Histologically confirmed prostate cancer. Small cell/neuroendocrine differentiated allowed but not required for study participation.
• Progressive metastatic prostate cancer (as defined below in Item #5) despite castrate levels of testosterone (< 50 ng/dL).
• Patients may have either non-measurable disease OR measurable disease
• Progressive disease during (or within 4 weeks of completion) with abiraterone, enzalutamide, and/or ARN-509 based on any one of the following: 1. For patients with measurable disease, progression by the RECIST criteria. 2. PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart. If the confirmatory PSA (#3) value is less (i.e., #3b) than the screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression for the purposes of eligibility. 3. Radionuclide bone scan: At least two new foci consistent with metastatic lesions
• Testosterone < 50 ng/dL. Patients must continue primary androgen deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy.
• Patients treated with first generation anti-androgen as most recent systemic therapy (bicalutamide, nilutamide) must have at least 4 weeks elapsed from treatment discontinuation to start of protocol therapy with evidence of disease progression by PCWG2 criteria following discontinuation of prior anti-androgen.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Patient has adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute neutrophil count ≥ 1.5 × 109/L.
• Platelets ≥ 100 × 109/L.
• Hemoglobin ≥ 9 g/dl.
• Potassium, total calcium (corrected for serum albumin) and magnesium within normal limits for the institution or corrected to within normal limits before first dose of study medication.
• International normalized ratio (INR) ≤ 1.5 unless on direct thrombin inhibitor at time of study entry.
• Serum creatinine ≤ 1.5mg/dL or estimated creatinine clearance ≥ 50 ml/min
• In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN). If the patient has liver metastases, ALT and AST <5 x ULN
• Total bilirubin < ULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with well-documented Gilbert's Syndrome.
• No other systemic therapies for prostate cancer within 28 days or 5 half-lives, whichever is shorter, prior to day 1 of study therapy.
• Sexually active males must use a condom during intercourse while taking the drug and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Fertile males must use a condom with spermicide (double barrier method).
• Age ≥ 18 years
• Written informed consent must be obtained prior to any screening procedures and according to local guidelines.

Exclusion Criteria:

• Patient has a known hypersensitivity to ribociclib or any of its excipients, or prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitor.
• Prior chemotherapy for metastatic castration-resistant prostate cancer. Chemotherapy administered in the castration-sensitive setting is allowed provided last dose of chemotherapy was greater than 6 months prior to study entry
• Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal cell skin cancer, squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
• Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.
• Baseline screening for CNS metastases is not required unless presence of signs and/or symptoms of involvement
• Patient is not able to swallow oral medication and/or has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or significant small bowel resection).
• Clinically significant, uncontrolled heart disease and/or recent events including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 12 months prior to screening
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) obtained during Screening.
• History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening. Patients with rate-controlled atrial fibrillation or flutter are permitted.
• Bradycardia (heart rate < 50 bpm at rest), by ECG or pulse, at screening
• Congenital long QT syndrome or family history of long QT syndrome
• Any of the following abnormalities on screening 12-lead ECG:
• QT interval with Fridericia's correction (QTcF) > 450 msec
• Bradycardia (heart rate < 50 bpm at rest)
• Tachycardia (heart rate > 100 bpm at rest)
• PR interval > 220msec,
• QRS interval >109 msec
• Documented cardiomyopathy
• Systolic blood pressure >160 mmHg or <90 mmHg at screening
• AST and/or ALT > 1.5 x ULN with concomitant alkaline phosphatase > 2.5 x ULN
• Patient receiving any of the following medications within 7 days of day 1 of study treatment.
• Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
• That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
• That have a known risk to prolong the QT interval or induce Torsades de Pointes.
• Herbal preparations/medications
• Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study drug at a dose greater than the equivalent of 10 mg prednisone/day, or who have not fully recovered from the side effects of such treatment
• The following uses of corticosteroids are permitted: short duration (<5 days) of systemic corticosteroids; any duration of topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
• Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, direct thrombin inhibitors, low molecular weight heparin (LMWH) or fondaparinux is allowed.
• Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer
• Major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).
• Patient who has received radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia), and/or in whom ≥25% of the bone marrow was irradiated.
• Patient has a known history of HIV infection (testing not required)
• Patient has not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAE version 4.03 to less than or equal to Grade 1 (Exception to this criterion: patients with grade 1 taxane-induced neuropathy, any grade of alopecia, amenorrhea or other toxicities not considered a safety risk for the patient as per investigator's discretion, are allowed to enter the study).
• Patients with chronic liver disease with a Child-Pugh score B or C.
• Patients with serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
• Patients with severe psychiatric illness/social situations that would limit compliance with study requirements in the judgment of study investigator.
• History of bleeding diathesis. Patients receiving anti-coagulation must be able safely interrupt treatment for tumor biopsy (Phase 2 only)
• Patient has a history of non-compliance to medical regimen or inability to grant consent

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Condition: Metastatic Castration Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03752099

Sponsor: Veru Inc.

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• To be included in this study, patients should meet all of the following criteria: • Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Patients >18 years of age.
• Histological or cytologic proof of adenocarcinoma of the prostate.
• Radiographic evidence of metastatic disease by CT scan or MRI and/or bone scan.
• Known castration resistant prostate cancer, defined according to PCWG3 criteria.
• Subjects who have metastatic castration resistant prostate cancer that have maintained ADT and have failed a novel androgen receptor agent (abiraterone or enzalutamide) defined as:
• Serum PSA progression of two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least two weeks apart. Or
• Documented bone lesions by the appearance of two or more new lesions on bone scintigraphy or dimensionally-measurable soft tissue metastatic lesion assessed by CT or MRI.
• Absolute PSA ≥2.0 ng/ml at screening.
• Prior chemotherapy for mCRPC:
• Phase 1b
• ONE prior taxane chemotherapy for mCRPC will be allowed during the Phase 1b portion of study as long as the last dose was more than four weeks prior to the first dose of study drug.
• Phase 2
• Prior chemotherapy for mCRPC is not allowed in the Phase 2 portion of the study. Prior chemotherapy for metastatic hormone sensitive prostate cancer will not qualify as a prior chemotherapy and the last dose must be >6 months prior to enrollment.
• Prior treatment with abiraterone, enzalutamide, bicalutamide, and/or ketoconazole is allowed. There is no limit on the maximum number or types of prior hormonal therapies received. The patients should be off prior therapy for at least two weeks (4 weeks off bicalutamide or nilutamide treatment) prior to first dose of study drug.
• ECOG performance status ≤2.
• Participants must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin 9.0 g/dL with no blood transfusion in the past 28 days.
• Absolute neutrophil count (ANC) 1.5 x 109/L.
• Platelet count 100 x 109/L.
• Total bilirubin ≤1.5 x institutional upper limit of normal (ULN) (or <2.5 x ULN for patients with known Gilberts disease).
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT))/Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤2.5 x institutional upper limit of normal. Note: Patients with elevations in bilirubin, AST, or ALT should be thoroughly evaluated for the etiology of this abnormality prior to entry and patients with evidence of viral infection should be excluded.
• Participants must have a life expectancy >3 months.
• Male participants, and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination [see Appendix E for acceptable methods], throughout the period of taking study treatment and for at least 4 weeks after the last dose of VERU-111 to prevent pregnancy in a partner.
• Other than the metastatic prostate cancer, no evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin or other cancers treated with curative intent >3 years prior).
• Participants must agree to either refrain from prolonged exposure to the sun or agree to use at least SPF 50 on all exposed skin and protective clothing during prolonged sun exposure throughout participation in this study and/or treatment with VERU-111.

Exclusion Criteria:

• Patients that meet any of the criteria listed below will not be eligible for study entry:
• Histologic identification of small cell carcinoma of the prostate or neuroendocrine pathology in either biopsy or prostatectomy tissue.
• Has received external-beam radiotherapy within the last 2 weeks prior to start of study treatment.
• Patients receiving full dose anticoagulation therapy are not eligible for study.
• Patients with prior history of a thromboembolic event within the last 6 months.
• Participation in another clinical study with an investigational product during the last 4 weeks/28 days.
• Patients should be excluded if they have had prior systemic treatment with two prior taxane chemotherapies for advanced prostate cancer. No limit to other prior therapies.
• Concurrent use of other anticancer agents (see Appendix G) or treatments, with the following exceptions: o Ongoing treatment with denosumab (Prolia) or bisphosphonate (e.g., zoledronic acid) is allowed. Ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed.
• Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment.
• Patients are excluded if they have active known brain metastases or leptomeningeal metastases.
• Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
• History of severe hypersensitivity reaction to any taxane chemotherapy.
• Has imminent or established spinal cord compression based on clinical findings and/or MRI.
• Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous.
• Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
• Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease, or any psychiatric disorder that prohibits obtaining informed consent.
• Total bilirubin levels > ULN or OR AST/ALT levels >1.5xULN with WITH concomitant alkaline phosphatase levels >2.5xULN. The following exclusion criterion is added to the Phase 1b portion of the study only: • Patients with substantial visceral disease who require immediate treatment with cytotoxic therapy

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Condition: Metastatic Castrate-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02607228

Sponsor: Gilead Sciences

Phase: Phase 1/Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Key Inclusion Criteria:

• Histologically or cytologically confirmed prostate cancer (individuals with primary neuroendocrine carcinoma of prostate are excluded)
• Must have documented progressive disease by meeting at least one of the Prostate Cancer Working Group 2 Criteria
• Castration resistant disease defined as ongoing androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy and serum testosterone level ≤ 1.73 nmol/l (50 ng/dL) at screening visit. Individuals who have not had a bilateral orchiectomy must have a plan to maintain effective GnRH-analogue therapy for the duration of the trial.
• Metastatic disease documented by bone lesions on bone scan or by measurable soft tissue disease by CT/MRI. Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
• Adequate organ function defined as follows:
• Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (without platelet transfusion or any growth factors within previous 7 days of the hematologic laboratory values obtained at screening visit)
• Hepatic: Aspartate transaminase (AST) / Alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN
• Renal: Serum Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min as calculated by the Cockroft-Gault method
• Coagulation: International Normalized Ratio (INR) ≤ 1.2

Key Exclusion Criteria:

• Known brain metastasis or leptomeningeal disease
• Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of Cycle 1 Day 1
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of GS-5829, including any unresolved nausea, vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1
• Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 21 days or 5 half-lives, whichever is longer, of study drug dosing (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t1/2 > 10 days); concurrent use of an luteinizing hormone releasing hormone (LHRH) agonist is permitted for all individuals and ongoing enzalutamide is required in Group 3.
• History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 450 ms).
• Prior exposure to bromodomain (BET) inhibitors
• Clinically significant bleeding within 28 days of Cycle 1 Day 1
• Known human immunodeficiency virus (HIV) infection
• HBsAg positive
• Hepatitis C virus (HCV) antibody positive
• Use of moderate/strong cytochrome P450 (CYP)3A4 inhibitors or moderate/strong CYP3A4 inducers within 2 weeks prior to the first dose of study drug (with the exception of enzalutamide in the combination arms)
• Evidence of bleeding diathesis
• History of hemoptysis of ≥ 2.5 mL/1 teaspoon within 6 months of Cycle 1 Day 1
• History of high grade esophageal or gastric varices
• Anticoagulation/antiplatelet therapy within 7 days of Cycle 1 Day 1, including low molecular weight heparin, or warfarin. NOTE: Other protocol defined Inclusion/

Exclusion Criteria:

1. may apply.

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Condition: Metastatic Castration Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04104893

Sponsor: VA Office of Research and Development

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Subject must be 18 years of age or older at the time the Informed Consent is signed.
• The subject (or legally acceptable representative if applicable) must provide written informed consent for the trial.
• Pathologic diagnosis of prostate cancer of adenocarcinoma or small cell histology.
• Metastatic disease as documented by technetium-99m (99mTc) bone scan or metastatic lesions by computed tomography (CT) or magnetic resonance imaging (MRI) scans (visceral or lymph node disease). CT-portion of FDG-PET/CT or scan may be used for eligibility. NaF PET-CT is an alternative to 99mTc bone scan. If lymph node metastasis is the only evidence of metastatic disease, it must be 1.5 cm in short axis and above the level of the iliac bifurcation. Imaging studies for the purpose of determining eligibility must be completed within 60 days of Day 1.
• Progressive castration resistant prostate cancer as defined by serum testosterone < 50 ng/mL and one of the following:
• PSA progression confirmed per Prostate Cancer Clinical Trials Working Group (PCWG3),
• Radiographic progression of soft tissues according to Response Evaluation Criteria in Solid Tumors, version 1.1 (iRECIST 1.1) modified based on PCWG3, or radiographic progression of bone according to PCWG3.
• Prior use of a novel AR signaling inhibitor for 4 weeks, including abiraterone acetate plus prednisone/prednisolone, enzalutamide, apalutamide, and/or darolutamide. NOTE: These AR signaling inhibitors may have been used for mCSPC, M0CRPC, and/or mCRPC.
• Ongoing surgical or medical castration, with testosterone levels of <50 ng/dL. If the subject is being treated with GnRH analogs (subject who has not undergone bilateral orchiectomy), this therapy must have been initiated at least 30 weeks prior to initiation of pembrolizumab and must be continued throughout the study.
• ECOG PS grade of 0-1.
• Metastatic lesion that is amenable to biopsy and performed within 180 days of Day 1.
• dMMR or CDK12-/- as determined by somatic tumor DNA NGS.
• Either monoallelic or biallelic inactivation of CDK12 on NGS is considered sufficient for eligibility purposes.
• MMR genes include: MLH1, MSH2, MLH3, PMS1, MSH6, and PMS2.
• dMMR is established by MSI-H on NGS. However, for "weak" MMR genes, inclusive of PMS2 and MSH6, monoallelic inactivation will be allowed for eligibility purposes if and only if there is at least MSI-low or hypermutation that is concomitantly present.
• If there is biallelic inactivation of "strong" MMR genes (MLH1 and MSH2), then patients must manifest MSI-H. However, if the tumor DNA utilized for MSI analysis was obtained > 6 months prior to NGS, then the NGS should be repeated to determine if MSI-H has developed. Monoallelic inactivation of "strong" MMR genes will be allowed if MSI-H is present; in this scenario, it is presumed that biallelic inactivation is present but the second inactivating event was not detected due to technical issues such as low sensitivity for copy loss.
• Adequate organ function:
• Hemoglobin (hgb) > 9.0 g/dL,
• Absolute neutrophil count (ANC) > 1500/ uL,
• Platelets > 100,000/ uL,
• Total bilirubin 1.5 x ULN OR direct bilirubin ULN for participants with total bilirubin levels >1.5 x ULN
• ALT and AST 2.5 x ULN ( 5 x ULN for participants with liver metastases) (Child-Pugh class A and B allowed; Child-Pugh class C is excluded).
• Creatinine < (2.0 mg/dL) during screening evaluation (>2.0 is allowed if EGFR >30 mL/min/1.73 m2).
• Subject must agree to use contraception during the treatment period plus an additional 120 days after the last dose of study treatment and must refrain from donating sperm during this period.

Exclusion Criteria:

• Brain metastases.
• Prior treatment with an anti-PD1, anti-PDL1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Anti-neoplastic therapies for prostate cancer must be completed > 2 weeks prior to Day 1 (initiation of pembrolizumab); chemotherapy must be completed > 4 weeks prior to Day 1.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to [randomization /allocation]. Note: Participants must have recovered from all AEs due to previous therapies to Grade 1 or baseline. Participants with Grade 2 neuropathy may be eligible.
• Herbal and non-herbal products that may decrease PSA levels other than medical castration and megestrol (up to 40 mg/day is allowed) for hot flashes.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation ( 2 weeks of radiotherapy) to non-CNS disease.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• If a subject has undergone major surgery, they must have recovered adequately from the toxicities or complications from the intervention within 4 weeks prior to starting therapy.
• History of non-prostate active malignancy requiring treatment in the 24 months prior to Day 1 except for non-muscle invasive urothelial cancer and non-melanoma skin cancer.
• Active infection or conditions requiring treatment with antibiotics.
• Immunosuppressive doses of systemic medications, such as corticosteroids (doses > 10 mg/day prednisone or equivalent), within 2 weeks of Day 1.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Active autoimmune disease or a documented history of autoimmune disease that requires immunosuppressive medications within the last two years (e.g., chronic steroids, methotrexate, tacrolimus, etc.).
• Active or chronic hepatitis B or hepatitis C disease as determined by hepatitis B surface antigen (HBsAg), hepatitis B core antibody, or hepatitis C antibody (anti-HCV) positivity at screening. If positive, further testing of quantitative levels to rule out active infection is required.
• History of positive test for human immunodeficiency virus (HIV). NOTE: Hepatitis B and C and HIV testing is NOT required during screening.
• Vaccinated with a live vaccine within 30 days of enrollment.
• Has severe hypersensitivity ( Grade 3) to pembrolizumab and/or any of its excipients.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Subject is planning to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.

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Condition: Hormone-Resistant Prostate Cancer, Metastatic Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02985021

Sponsor: Seattle Institute for Biomedical and Clinical Research

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Patients meeting the following inclusion criteria will be eligible to participate in this study: 1. Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information. 2. Age > 18 years 3. Known prostate cancer 4. Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy. 5. Castration resistant prostate cancer as defined by serum testosterone < 50ng/ml and one of the following:
• PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart.
• Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors).
• Progression of metastatic bone disease on bone scan with > 2 new lesions. 6. Prior therapy with abiraterone acetate, enzalutamide, or docetaxel. There is no limit to the number of prior treatment regimens. 7. Presence of metastatic disease on scans. 8. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2. 9. Life expectancy >12 weeks. 10. No prior malignancy is allowed except:
• Adequately treated basal cell or squamous cell skin cancer or
• In situ carcinoma of any site or
• Other adequately treated malignancy for which the patient has been disease-free for at least one year (any prior chemotherapy is allowed). 11. Patients must have adequate organ and marrow function as defined below obtained within 14 days prior to start of therapy: 1. Absolute neutrophil count >1.5 x 109 cells/L 2. Hgb > 9.0 g/dL 3. Platelets >100,000 x 109/L 4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels < 1.5 x Upper Limit of Normal (ULN) 12. Presence of germline inactivation of BRCA1, BRCA2, ATM OR one of the following:
• Patients with clearly deleterious germline mutations of other genes involved in homologous DNA repair may be included at the investigator's discretion.
• Patients with homozygous inactivation of genes involved in homologous recombination from primary or metastatic tumor as assessed by a Clinical Laboratory Improvement Amendments (CLIA) level assay for DNA sequencing may be included.
• Patients with a signature of homologous recombination deficiency ("BRCAness") in primary or metastatic tissue may be included (VA Puget Sound only).

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from the study: 1. Currently receiving active therapy for other neoplastic disorders. 2. Histologic evidence of small cell carcinoma (morphology alone
• immunohistochemical evidence of neuroendocrine differentiation without morphologic evidence is not exclusionary). 3. Prior treatment with platinum-based chemotherapy for prostate cancer. 4. Known parenchymal brain metastasis. 5. Active or symptomatic viral hepatitis or chronic liver disease. 6. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 35 % at baseline, if done. 7. Treatment with an investigational therapeutic within 30 days of Cycle 1. 8. Patients with dementia/psychiatric illness/social situations limiting compliance with study requirements or understanding and/or giving of informed consent are not eligible 9. Any medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained are not eligible.

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Condition: Castrate Resistant Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, Prostate Cancer, Prostate Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05766371

Sponsor: University of California, San Francisco

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• 1. Histologically confirmed prostate adenocarcinoma that is progressive metastatic castration-resistant prostate cancer by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria at the time of study entry. 2. Male participants who are at least 18 years of age on the day of signing informed consent. 3. Castrate level of serum testosterone at study entry (< 50 ng/dL). Note: Patients without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study. 4. Have received at least one prior line of taxane chemotherapy, or are unfit for, or refuse taxane chemotherapy. Note: Taxane chemotherapy administered in the Castration Sensitive Prostate Cancer (CSPC) or Castration Resistant Prostate Cancer (CRPC) setting is allowed. 5. Prior progression on at least one second generation androgen signaling inhibitor including abiraterone, apalutamide, darolutamide, and/or enzalutamide. 6. Adverse events related to prior anti-cancer treatment (excluding LHRH analogs) must have recovered to Grade <= 1 (except for any grade alopecia and grade <= 2 neuropathy). 7. Prior radiotherapy is allowed if the last radiotherapy treatment was greater than 2 weeks from start of study treatment on cycle 1, day 1 (C1D1). Note- Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (<=2 weeks of radiotherapy) to non-central nervous system (CNS) disease. 8. At least one Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) (PSMA PET) avid lesion on screening PSMA PET. A positive lesion is defined as uptake above background liver. 9. Eastern Cooperative Oncology Group (ECOG) performance status <= 1 (Karnofsky >= 70%). 10. Demonstrates adequate organ function as defined below: 1. Adequate bone marrow function:
• absolute neutrophil count >=1,500/microliter (mcL)
• platelets >=100,000/mcL
• hemoglobin > 9.0 g/dL 2. Adequate hepatic function:
• total bilirubin <= 1.5 x upper limit of normal (ULN). In patients with known or suspected Gilbert's disease, direct bilirubin <= ULN
• aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) <= 2.5 x institutional ULN (<= 5 x ULN in patients with liver metastases)
• alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <= 2.5 x institutional upper limit of normal (<= 5 x ULN in patients with liver metastases) 3. Adequate renal function:
• creatinine <= 1.5 x within institutional upper limit of normal OR
• creatinine clearance Glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2, calculated using the Cockcroft-Gault equation or 24 hour urine collection. 11. Patients must use appropriate methods of contraception during study treatment and for at least 6 months after last study treatment. Patients who are sexually active should consider their female partner to be of childbearing potential if she has experienced menarche and is not postmenopausal (defined as amenorrhea > 24 consecutive months) or has not undergone successful surgical sterilization. Even women who use contraceptive hormones (oral, implanted, or injected), an intrauterine device, or barrier methods (diaphragms, condoms, spermicide) should be considered to be of childbearing potential. Patients who have undergone vasectomy themselves should also be considered to be of childbearing potential. Acceptable methods of contraception include continuous total abstinence, or double-barrier method of birth control (e.g., condoms used with spermicide, or condoms used with oral contraceptives). Periodic abstinence and withdrawal are not acceptable methods of contraception. 12. Patients must provide consent to comply to recommended radioprotection precautions during study. 13. Patients willing to undergo tumor biopsy and have at least one lesion safely accessible to tumor biopsy. Bone or soft tissue lesion is allowed. 14. Patients with previously treated brain metastases are eligible provided the following criteria are all met: 1. Last treatment was > 28 days prior to C1D1. 2. No evidence of new/progressive brain metastases is observed on magnetic resonance imaging (MRI) obtained during screening window 3. Patient is clinically stable without requirement of steroid treatment for at least 14 days prior to first dose of study treatment on C1D1. 15. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. 16. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. De novo small cell neuroendocrine prostate cancer will not be allowed due to putative lower PSMA expression in this tumor subtype. Note-Treatment-emergent small cell neuroendocrine prostate cancer detected in metastatic tumor biopsy is not excluded.
2. Soft tissue lesions (lymph nodes > 1.5 centimeter (cm) in short axis, visceral/soft tissue lesions > 1 cm) on screening Computerized tomography (CT) that are negative on PSMA PET. Note: Negative lesions on PSMA PET are defined as those with uptake below the background liver.
3. Has received other systemic anti-cancer therapies administered within 14 days, or 5 half-lives, whichever is shorter, prior to initiation of study treatment. Note: LHRH analogues are the exception.
4. Untreated brain metastases at study entry.
5. Receipt of prior PSMA-directed treatment (e.g., radiotherapy, immunotherapy, or antibody-drug conjugate).
6. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-Programmed cell death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX 40, CD137).
7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment on C1D
8. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
9. Receipt of > 2 lines of prior taxane-based chemotherapy.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
11. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) or treatment with drugs (e.g., neomercazole, carbimazole, etc.) that function to decrease the generation of thyroid hormone by a hyper-functioning thyroid gland (e.g., in Graves' disease) is not considered a form of systemic treatment of an autoimmune disease.
12. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a prednisone equivalent dose of > 10 mg daily or other form of immunosuppressive therapy within 7 days prior to first dose of study drug.
13. Has a history of (non-infectious) ≥ grade 2 pneumonitis/interstitial lung disease that required steroids within past 2 years or has current ≥ grade 1 pneumonitis/ interstitial lung disease at the time of study enrollment.
14. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug on C1D
15. Note-Administration of a killed vaccine is allowed.
16. Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
17. Has clinically significant cardiovascular disease including, but not limited to:
18. Uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure.
19. Uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months before study entry.
20. Clinically significant arrhythmias not controlled by medication. Note: Chronic rate controlled or paroxysmal atrial fibrillation/flutter is not an exclusion to study participation.
21. Prior external beam radiation involving > 25 percent (%) of bone marrow or within 14 days of start of protocol therapy on C1D
22. Major surgery within 28 days of study treatment. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment on C1D
23. Minor procedures (e.g., biopsy, cataract surgery, stent placement, endoscopy) are not considered major surgery.
24. Has an active infection requiring intravenous antibiotics within 7 days prior to C1D
25. Has a known history of human immunodeficiency virus (HIV) infection. Note: Screening not required.
26. Has a known history of Hepatitis B infection (defined as Hepatitis B surface antigen (HBsAg) reactive) or known active Hepatitis C virus infection (defined as (HCV RNA) [qualitative] detected, with the following exceptions:
27. participants who are HbsAg positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to study entry
28. participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to study entry.
29. Has a known history of active Bacillus Tuberculosis (TB).
30. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
31. History of bleeding diathesis and currently on anti-coagulation therapy that cannot be safely discontinued for the tumor biopsy procedure.
32. Any condition that, in the opinion of the Principal Investigator, would impair the participant's ability to comply with study procedures.

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Condition: Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01881867

Sponsor: Fred Hutchinson Cancer Research Center

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)
• Patients must have successfully completed therapy with sipuleucel-T within 3-7 days of planned CYT107 study drug treatment
• Assessable disease with a positive bone scan and/or measurable disease on computed tomography (CT) scan and/or magnetic resonance imaging (MRI) of the abdomen and pelvis
• Prior orchiectomy or must be on ongoing luteinizing hormone-releasing hormone (LHRH) agonist or antagonist (e.g., degarelix) therapy
• No ongoing anti-androgen therapy; patients must be off anti-androgen therapy for at least 30 days
• Patients receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease prostate specific antigen (PSA) levels (e.g. saw palmetto, PC-SPES), or any systemic corticosteroid, must discontinue the agent for at least 30 days prior to study treatment
• Absolute neutrophil count (ANC) >= 1500/uL
• Bilirubin < 1.5 x upper limit of normal (ULN)
• Hemoglobin >= 10 g/dL
• Platelets >= 100,000/mcL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Creatinine clearance >= 60 mL/min by the Cockcroft-Gault equation
• Testosterone =< 50 ng/dL (documented at any time while on LHRH agonist or antagonists or s/p orchiectomy)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or a Karnofsky performance status of >= 80%
• Life expectancy of at least 6 months
• Prior local radiation therapy must be completed at least 30 days prior to enrollment and the patient must have recovered from all toxicity
• Prior "systemic" radiopharmaceuticals (strontium, samarium, radium 223 dichloride) must be completed >= 8 weeks prior to enrollment
• Patients must agree to use 2 methods of adequate contraception for the duration of study participation, and for four months after discontinuing therapy
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior chemotherapy for castration resistant prostate cancer; neoadjuvant chemotherapy and chemotherapy given for hormone sensitive prostate cancer are allowed
• Prior investigational immunotherapy
• Prostate cancer pain requiring regularly scheduled narcotics
• Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression
• Current treatment with systemic steroid therapy (inhaled/topical steroids are acceptable); systemic corticosteroids must be discontinued for at least 30 days prior to first CYT107 injection
• Known central nervous system metastases
• Documented cirrhosis or documented acute hepatitis; Note: a positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antibody [HBsAb] positive and hepatitis B core antibody [HBcAb] negative), or a fully resolved acute hepatitis B virus (HBV) infection is not an exclusion criterion
• History of severe asthma, as defined by prior or current use of systemic corticosteroids for disease control, with the exception of physiological replacement doses of cortisone acetate or equivalent, as defined by a dose of 10 mg or less
• Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
• Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
• Concurrent or prior malignancy except for the following:
• Adequately treated basal or squamous cell skin cancer
• Adequately treated stage I or II cancer from which the patient is currently in complete remission
• Any other cancer from which the patient has been disease-free for 5 years
• Known human immunodeficiency virus (HIV) or other history of immunodeficiency disorder; HIV-positive patients on combination antiretroviral therapy are ineligible
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g. infectious) illness
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of CYT107 hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CYT107
• Patients who have received prior immunosuppressive therapy within 30 days prior to enrollment
• Active (as defined by requiring immunosuppressive therapy) or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy)
• Patients who have received hepatotoxic drugs less than 7 days prior to enrollment
• Patients who have received prior biologic agents less than 30 days prior to enrollment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who have a history of any hematopoietic malignancy
• History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume [FEV] > 60% of predicted for height and age required in patients with prolonged smoking history or symptoms of respiratory dysfunction)

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Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02463799

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• 1. Written informed consent provided prior to initiation of study procedures 2. Age ≥ 18 years 3. Histologically documented adenocarcinoma prostate cancer confirmed by a pathology report from prostate biopsy or a radical prostatectomy specimen. If prostatic tumor is of mixed histology, > 50% of the tumor must be adenocarcinoma 4. Bone metastases as manifested by one or more lesions on a bone scan performed within 2 months of screening 5. Castrate-resistant prostate cancer, in the setting of castrate levels of testosterone (≤ 50 ng/dL), defined as current or historical evidence of disease progression concomitant with surgical castration or androgen deprivation therapy (ADT), as demonstrated by two consecutive rises in PSA OR new lesions on bone scan:
• PSA progression will be defined as 2 rising PSA values compared to a reference value, measured at least 7 days apart and the second value is ≥ 2 ng/mL [1]. It must be documented within 2 months of screening.
• Appearance of one or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the precastration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression. It must be documented within 4 months of screening 6. Serum PSA ≥ 2.0 ng/mL 7. Screening ECOG perf status ≤ 1 8. Asymptomatic or minimally symptomatic disease (no narcotic analgesic; other analgesics use is allowed) 9. Prior abiraterone and enzalutamide are permitted, but not required 10. Concurrent osteoclast-inhibitory therapies (zoledronic acid, denosumab) are permitted if patients have been on a stable dose for at least 1 month 11. Adequate screening hematologic, renal, and liver function as evidenced by laboratory test results within the following ranges ≤ 28 days prior to registration:
• Absolute neutrophil count (ANC) ≥ 1.5 x109/L
• Platelet count ≥ 100 x109/L
• Hemoglobin ≥ 10.0 g/dL
• Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Creatinine ≤ 1.5 x ULN
• Albumin > 25 g/L

Exclusion Criteria:

1. The presence of known lung or liver metastases greater than 1.0 cm in the long axis diameter
2. The presence of lymphadenopathy greater than 3 cm in the short-axis diameter
3. The presence of known brain metastases
4. Spinal cord compression, imminent long bone fracture, or any other condition that, in the opinion of the investigator, is likely to require radiation therapy and/or steroids for pain control during the active phase
5. Previous treatment with chemotherapy for mCRPC (adjuvant chemotherapy is permitted), or chemotherapy for any reason within 2 years prior to registration
6. Intention to receive chemotherapy within 6 months after enrollment in protocol therapy
7. History of radiation therapy, either via external beam or brachytherapy within 28 days prior to registration
8. Systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within previous 24 weeks
9. Prior history of other cancers (except non-melanoma skin cancers or low-grade low-stage urothelial cancers)
10. Use of prednisone or equivalent systemic corticosteroid within 2 weeks of treatment. Use of inhaled, intranasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to prevent or treat IV contrast reactions are allowed
11. Use of opioid analgesics for cancer-related pain
12. Use of experimental drug within 4 weeks of treatment
13. Uncontrolled medical conditions including diabetes, heart failure, COPD, ulcerative colitis, or Crohn's disease
14. Uncontrolled fecal incontinence
15. Any medical intervention, any other condition, or any other circumstance which, in the opinion of the investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives

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Condition: Castration-Sensitive Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05241860

Sponsor: Alliance for Clinical Trials in Oncology

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Histologic or clinical diagnosis of metastatic prostate cancer
• Must have had evidence of metastatic disease by bone scan, or nodal or visceral lesions on computed tomography (CT) or magnetic resonance imaging (MRI) prior to starting on intense antiandrogen therapy (ADT)
• Radiographic evidence of disease is not required at the time of enrollment
• No metastases to liver or to brain, as these represent aggressive variant disease biology for which intermittent treatment may not be favored
• Must currently be receiving intense ADT for metastatic hormone sensitive prostate cancer (mHSPC)
• Testosterone suppression (TS) with luteinizing hormone releasing hormone (LHRH)-agonist or LHRH-antagonist AND
• An approved secondary androgen receptor pathway inhibitor (ARPI) abiraterone, enzalutamide, or apalutamide (or darolutamide if approved for this indication)
• Must have remained on testosterone suppression for metastatic disease continuously (without treatment breaks) for 540-750 days (approximately 18 to 24 months) from time of first dose of LHRH agonist or antagonist by time of registration. A period of anti-androgen treatment prior to LHRH agonist or antagonist initiation is not included in the 540
• 750 days (approximately 18 to 24 months)
• Must have received treatment with ARPI for at least 360 days in total by time of A032101 registration. Treatment breaks from ARPI of up to 28 days are permitted (for example peri-procedural or for management of a temporary adverse event) as long as PSA did not rise while holding therapy
• Prior TS in the context of neoadjuvant/concurrent/adjuvant treatment with local therapy is permitted. Prior course(s) of intermittent TS for biochemical-only recurrence is permitted. However, if the patient previously received TS, metastatic progression for which intense ADT was initiated must have occurred during an off-treatment interval and with testosterone >= 150 ng/dL
• Prior local therapy for prostate cancer (either before or after diagnosis of metastatic disease) is permitted. Prior treatment with docetaxel chemotherapy for up to 6 cycles is permitted. Prior radiation therapy to metastatic sites (either for symptom palliation or for ablation of oligometastatic disease) is permitted

Exclusion Criteria:

• No history of surgical castration
• No history of ARPI use prior to diagnosis of mHSPC for which the patient is currently receiving intense ADT (such as in the neoadjuvant setting with prior local therapy)
• No current or prior treatment with experimental agents for metastatic hormone-sensitive prostate cancer
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Prior to initiating intense ADT
• Prostate specific antigen (PSA) >= 5 ng/ml
• Testosterone >= 150 ng/dl. Patients are permitted to enroll if testosterone was not measured prior to initiating intense ADT for mHSPC if they did not previously receive TS and were not known or suspected to be hypogonadal at the time
• At time of enrollment to A032101
• PSA < 0.2 ng/ml ** PSA values (measured in the same laboratory) must be stable or falling for 3 consecutive measurements
• i.e. any PSA rise must be followed by a decrease in PSA that is further decreased or stable on a 3rd measurement. Any patient with 2 consecutive rises in PSA values since achieving castrate level of testosterone is not eligible
• Testosterone < 50 ng/dl
• No current participation in a clinical study that does not allow for TS or ARPI interruption
• No patients with a "currently active" second malignancy * Patients with non-melanomatous skin cancer, superficial bladder cancer, cancer not needing active therapy for at least 2 years, cancer for which the treating investigator deems the subject

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Condition: Prostatic Neoplasms, Castration-Resistant

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05169684

Sponsor: Bristol-Myers Squibb

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

Inclusion Criteria:

• Histologic confirmation of carcinoma of the prostate without small cell features
• Documented prostate cancer progression by Prostate Cancer Working Group 3 (PCWG3) criteria while castrate
• Evidence of metastatic disease documented by either bone lesions on radionuclide bone scan and/or soft tissue lesions on computed tomography (CT)/magnetic resonance imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or bilateral orchiectomy (i.e., surgical or medical castration) confirmed by testosterone level ≤ 1.73 nmol/L (50 ng/dL) at the screening visit
• Chemotherapy-naive for metastatic castration-resistant prostate cancer (mCRPC) and have received at least one novel antiandrogen therapy (NAT) Exclusion Criteria:
• Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to treatment assignment in Part 1 or randomization in Part 2
• Untreated central nervous system (CNS) metastases
• Leptomeningeal metastases
• Active, known or suspected autoimmune disease Other protocol-defined inclusion/

Exclusion Criteria:

• Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to treatment assignment in Part 1 or randomization in Part 2
• Untreated central nervous system (CNS) metastases
• Leptomeningeal metastases
• Active, known or suspected autoimmune disease Other protocol-defined inclusion/exclusion criteria apply

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