|
|
|
|
|
|
|
PEER-TO-PEER CLINICAL CONVERSATIONS
|
|
|
|
|
|
|
MEVPRO-1 and MEVPRO-2 Trials of EZH2 Inhibitor Mevrometostat in mCRPC
|
Neeraj Agarwal, MD, FASCO
Neeraj Agarwal presents the MEVPRO-1 and MEVPRO-2 trial designs, grounding them in phase 2 data showing that mevrometostat, an EZH2 inhibitor, added to enzalutamide improved rPFS from 6 months to 14.3 months versus enzalutamide alone in 80 abiraterone-pretreated mCRPC patients.
|
|
|
|
|
|
|
|
|
|
|
|
AR Degraders, T-Cell Engagers, and EZH2 Inhibitors in Prostate Cancer Pipeline
|
|
Maha Hussain, MD, FACP, FASCO
|
| Maha Hussain surveys emerging prostate cancer therapies across disease states. An AR degrader under investigation in a phase 3 study called rechARge showed a median PFS of 16.5 months in chemotherapy-naive mCRPC patients and approximately 5.5 months in those with prior chemotherapy.
|
|
|
|
|
|
|
|
|
|
|
|
|
Navigating Treatment Decisions in Castration-Resistant Prostate Cancer
|
Karim Fizazi, MD, PhD
Karim Fizazi presents a practical framework for treatment selection in castration-resistant prostate cancer based on genomic findings, disease tempo, symptoms, and prior therapy. He reviews how HRR alterations, MSI-high or mismatch repair-deficient disease, and emerging biomarkers such as AR mutations and PTEN loss may guide treatment, while also addressing options for patients without an actionable genomic alteration.
|
|
|
|
|
|
|
|
|
|
|
| Mevrometostat in Advanced Prostate Cancer: Targeting EZH2 Across the Disease Continuum Through the MEVPRO Clinical Trial Program
|
| Zachary Klaassen, MD, MSc
|
| Zach Klaassen discusses mevrometostat, an oral, selective EZH2 inhibitor being evaluated in the MEVPRO phase III program to target epigenetic resistance mechanisms that sustain AR signaling and drive progression in advanced prostate cancer. The program includes MEVPRO-1, MEVPRO-2, and MEVPRO-3, all with rPFS by BICR as the primary endpoint.
|
|
|
|
|
|
| TALAPRO-3: Talazoparib + Enzalutamide Compared with Placebo + Enzalutamide for the Treatment of Patients with mCSPC Harboring HRR Gene Alterations |
| Neeraj Agarwal, MD, FASCO |
| In the phase III TALAPRO-3 trial of 599 patients with HRR gene-altered metastatic castration-sensitive prostate cancer receiving ADT, adding talazoparib to enzalutamide significantly improved investigator-assessed radiographic progression-free survival vs placebo + enzalutamide, with benefits seen in BRCA-mutated and non-BRCA HRR-altered subgroups and across disease volumes and stages. |
|
|
|
|
|
| A Phase 1, First-in-Human Study Evaluating the Safe, Pharmacokinetics, and Efficacy of ABBV-969 in Patients with mCRPC
|
| Tanya Dorff, MD
|
| ABBV-9969 is a first-in-class, dual-target antibody–drug conjugate binding PSMA and STEAP1 that delivers a topoisomerase-1 inhibitor payload and showed promising efficacy in a first-in-human phase 1 trial of heavily pretreated mCRPC patients. At doses ≥3 mg/kg, 67% achieved PSA50 responses, the objective response rate was 45%, and median radiographic PFS was 15.3 months, with durable responses up to ~11 months.
|
|
|
|
|
|
| Masked Antibody Therapeutics in Genitourinary Malignancies: Expanding the Therapeutic Window Through Tumor-Selective Activation
|
| Evan Yu, MD
|
| Evan Yu discusses Masked antibody therapeutics engineer tumor-selective activation in genitourinary malignancies by concealing a parent antibody or T-cell engager with protease-cleavable masking peptides that are removed in the tumor microenvironment, thereby widening the therapeutic window and reducing on-target, off-tumor toxicity of targets such as PSMA, HER2, EGFR, and EpCAM.
|
|
|
|
|
|
| The Diversity and Clinical Relevance of Germline DNA Damage Repair Gene Variants in 3005 Patients with Metastatic Prostate Cancer
|
| Sofie Tolmeijer, PhD
|
| In 3,005 metastatic prostate cancer patients, germline DDR variants were found in 9%, with BRCA2, ATM, and CHEK2 most common, and structural variants accounting for a substantial fraction of alterations in MSH2/6 and FANCA but only 2% of BRCA2 variants. BRCA2 carriers showed more aggressive disease—higher Grade Group ≥4, faster progression to castration resistance, and markedly shorter median overall survival.
|
|
|
|
|
|
|
|
|
|
|
