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PEER-TO-PEER CLINICAL CONVERSATIONS |
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| Innovative Therapies in GU Cancers: Promising Targets in Urothelial and Kidney Cancer |
| Jonathan Rosenberg, MD |
| Alicia Morgans speaks with Jonathan Rosenberg about two novel therapies presented at ESMO 2024. The discussion centers on BL-B01D1, a bispecific antibody-drug conjugate targeting EGFR and HER3 in advanced urothelial cancer, which shows promising early results with a 40% response rate in previously treated patients. |
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| NKT2152: Promising New HIF-2 Alpha Inhibitor for Advanced Renal Cell Carcinoma |
| Eric Jonasch, MD |
| Eric Jonasch discusses data on NKT2152, a novel HIF-2 alpha inhibitor for clear cell renal cell carcinoma. The phase 1/2 study shows promising results in heavily pre-treated patients, with objective response rates around 25% and median progression-free survival of 7.4 months. |
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| Bladder Cancer Breakthroughs in SunRISe-1, AMBASSADOR, and VOLGA Trials |
| Maria De Santis, MD, PhD |
| Alicia Morgans interviews Maria De Santis about three studies: the SunRISe-1 trial for non-muscle-invasive bladder cancer, the AMBASSADOR study on adjuvant pembrolizumab for muscle-invasive urothelial carcinoma, and the VOLGA trial exploring ctDNA clearance as a biomarker. |
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Tumor Heterogeneity Selective Pressure – Why We Need New Targets?
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A. Oliver Sartor, MD
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| Oliver Sartor emphasizes the challenges of tumor heterogeneity in prostate cancer, highlighting how clonal evolution under treatment drives resistance and necessitates personalized approaches. He discussed the need for improved disease monitoring, novel therapeutic targets (e.g., DLL3, WNT pathways, and radioligand therapies), and a shift from over-reliance on AR-targeted therapies to combination strategies.
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AKT Inhibitors – Targeting PI3K/AKT/MTOR Signaling Axis
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Cora Sternberg, MD, FACP
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| The IPATential150 trial demonstrated that combining the AKT inhibitor Ipatasertib with abiraterone significantly improved rPFS in patients with PTEN-loss mCRPC, though benefits in the overall population were less pronounced. Biomarker precision and managing side effects like hyperglycemia and diarrhea are critical for optimizing outcomes. Future studies, like CAPItello-281, will further explore this pathway in prostate cancer, highlighting the need for personalized approaches in treatment. |
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| BL-B01D1-201: BL-B01D1, an EGFR x HER3 Bispecific Antibody-drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma
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| Dingwei Ye, MD, PhD
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| Dingwei Ye presented phase Ib/II trial results for BL-B01D1, an EGFR x HER3 bispecific antibody-drug conjugate, in advanced or metastatic urothelial carcinoma. The study found a 40.7% objective response rate and a high disease control rate (96.3%) at the 2.2 mg/kg dose, with particularly strong efficacy in second-line settings. BL-B01D1 demonstrated a favorable safety profile, manageable hematologic toxicities, and clinical activity across varying EGFR and HER3 expression levels, supporting further exploration in registrational trials.
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| Moving the Needle: Novel Targets and Refined Approaches in Genitourinary Cancers |
| Jonathan E. Rosenberg, MD |
| Jonathan Rosenberg discusses advances in genitourinary cancer treatment, focusing on two novel therapies. The bispecific antibody-drug conjugate BL-B01D1 showed promising efficacy in advanced urothelial carcinoma, especially as a second-line treatment, with a 40.7% response rate and a manageable safety profile. Additionally, NKT2152, a small-molecule HIF-2α inhibitor, demonstrated potential in heavily pre-treated clear cell RCC, achieving a 20-26% objective response rate and 9.2-month progression-free survival, warranting further investigation in advanced RCC and beyond. |
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| ADC Toxicity, Management and Clinical Trial Updates
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| Srikala Sridhar, MD, MSc, FRCPC
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| Srikala Sridhar presents updates on antibody-drug conjugates (ADCs) in bladder cancer, highlighting enfortumab vedotin and sacituzumab govitecan's efficacy and distinct side effect profiles, including skin toxicity, neuropathy, and hyperglycemia. Enfortumab vedotin, particularly in combination with pembrolizumab, has shown significantly improved survival in metastatic urothelial carcinoma. The presentation underscored the need for biomarkers and optimized treatment sequencing as ADCs expand into earlier bladder cancer stages.
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| NKT2152, a Novel Oral HIF-2α Inhibitor, in Participants with Previously Treated Advanced Clear Cell RCC: Preliminary Results of a Phase 1/2 Study |
| Eric Jonasch, MD |
| Eric Jonasch presents the early results from a phase 1/2 trial of NKT2152, an oral HIF-2α inhibitor, in patients with advanced clear cell RCC. Among 100 patients, the objective response rate was 20%, with a progression-free survival (PFS) of 7.4 months, while patients without prior mTOR inhibitor therapy achieved a PFS of 12.7 months. NKT2152 showed manageable safety, linear pharmacokinetics, and sustained erythropoietin suppression, supporting its continued evaluation in high-risk RCC cases. |
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| Emerging Frontiers in Advanced Bladder Cancer: Paradigm Shifts in Diagnosis and Treatment |
| Shilpa Gupta, MD |
| Recent updates in advanced urothelial cancer highlight significant treatment advances, especially with enfortumab vedotin and pembrolizumab showing improved progression-free survival, overall survival , and quality of life compared to chemotherapy. EV-P has been established as the preferred first-line treatment by both the NCCN and ESMO, now regarded as the new standard of care. Additional promising results come from CheckMate 901 and JAVELIN Bladder 100, which also emphasize the importance of personalized treatment approaches, particularly for patients with unique clinical profiles and varying chemotherapy eligibility. |
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| LEGEND: A Phase 1/2 Study of EG-70 (Detalimogene Voraplasmid) Intravesical Monotherapy for Patients with BCG-Unresponsive NMIBC with CIS |
| Joan Palou, MD, PhD, FEBU, FRCS (Glas) |
| The LEGEND trial is a phase 1/2 study evaluating EG-70 (detalimogene voraplasmid) as an intravesical monotherapy for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). EG-70 aims to stimulate a localized anti-tumor immune response within the bladder, minimizing systemic side effects. |
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| Randomized Phase 3 Trial of Neoadjuvant Durvalumab plus Chemotherapy Followed by Radical Cystectomy and Adjuvant Durvalumab in Muscle-Invasive Bladder Cancer (NIAGARA) |
| Thomas Powles, MBBS, MRCP, MD |
| The NIAGARA trial, presented at ESMO 2024, is the first randomized phase 3 study testing perioperative durvalumab (an immune checkpoint inhibitor) combined with neoadjuvant chemotherapy (NAC) in cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC). This trial aimed to improve long-term outcomes by priming anti-tumor immunity before surgery and addressing micrometastatic disease after surgery. |
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