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ESMO 2020

ESMO Virtual Congress 2020: Efficacy of BN-Brachyury + Bintrafusp Alfa + N-803 in Castration-Resistant Prostate Cancer: Results from a Preliminary Analysis of the Quick Efficacy Seeking Trial

(UroToday.com) Prostate cancer has relatively low rates of response to immunotherapy such as immune checkpoint blockade relative to other types of cancer. Strategies to improve the immune response against advanced prostate cancer are under evaluation. Jason M. Redman, MD, presented data from the Quick Efficacy Seeking Trial, designed to rapidly evaluate the safety and efficacy of BNVax (a poxviral vaccine targeted against brachyury, a pro-invasion/metastasis transcription factor) + bintrafusp alpha (a bidirectional fusion protein that blocks PD-L1 as well as sequesters TGF-beta isoforms) + N-803 (an IL-15 superagonist), together designed to engage multiple arms of the immune system in patients with castration-resistant prostate cancer.

Patients with castration-resistant prostate cancer (CRPC) (metastatic or nonmetastatic) were eligible if they had castrate levels of testosterone, had received chemotherapy more than 1 year prior for CRPC, or more than 3 months prior if castration-sensitive disease at that time. The primary endpoint was objective response rate or PSA decline greater than 30% sustained for more than 21 days. Progression was defined as radiographic progression or PSA increase of over 1 ng/mL confirmed by two values a week apart.

In the first arm of the study, CRPC patients were first treated with BNVax and bintrafusp alpha. After safety was established, a second arm of patients were treated with all agents. Patient demographics are shown below.

PatientDemographics_616MO_figure1.png

In the first arm of the BNVax plus bintrafusp, only 1 patient had a sustained prostate-specific antigen (PSA) response. The addition of N-803 resulted in 5 patients having a sustained PSA response and two of those patients also had a radiographic response.

Arm2.1_2.2_BNVax_Figure2.png

Most side effects were grade 1-2, including transient fever, chills and injection site reactions. Three patients in each arm had grade 3 adverse events (tumor hemorrhage, ACTH deficiency, pancreatitis, diabetes, cystitis and eosinophilia). No grade 4 events were observed. Of note, all four patients who developed ACTH deficiency (of any grade) were PSA responders.

In summary, this triple immunotherapy combination produced a PSA response rate of 55%, including 2 radiographic partial responses in patients who had progressed on standard of care anti-androgen therapy. The significance of isolated ACTH deficiency in PSA responders is unclear and requires further investigation.

Presented by: Jason M. Redman, MD, Assistant Research Physician, Cancer Immunotherapy Program, Genitourinary Malignancy Branch, Medical Oncology Service, National Cancer Institute, Bethesda, MD

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.