Endpoints and early efficacy signals from phase 1 and dose-expansion data

Dr. Agarwal asks Dr. Morgans to describe the key secondary endpoints of MEVPRO-1 and MEVPRO-2 and the efficacy signals seen so far. Dr. Morgans confirms that the primary endpoint for both trials is blinded independent central review-assessed radiographic progression-free survival (rPFS). Key secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response, prostate-specific antigen (PSA) response, safety, pharmacokinetics, circulating tumor DNA (ctDNA), and patient-reported outcomes—a broad constellation of measures relevant to clinicians and patients.

She then summarizes the supporting early-phase data. The phase 1 dose-escalation study reported a median rPFS of approximately 17 months, an ORR of 27.3%, and a confirmed PSA50 response rate of 14.9%. The randomized dose-expansion study—conducted in the post-abiraterone mCRPC setting—reported a median rPFS of 14.3 months with mevrometostat plus enzalutamide versus 6.2 months with enzalutamide alone (hazard ratio 0.51), an ORR of 26.7% versus 14.3%, and confirmed PSA50 of 34.1% versus 15.4%.

Dr. Agarwal interjects to emphasize the clinical context: enzalutamide alone after abiraterone typically delivers about 6 months of rPFS, exactly as seen in the control arm. The 14.3-month rPFS with the combination was the striking finding that motivated the phase 3 program. Dr. Morgans agrees that the suggested synergy and maintained androgen receptor pathway inhibitor sensitivity make this combination highly interesting.

In the next episode, "Safety profile and adverse event management with mevrometostat plus enzalutamide," Dr. Agarwal discusses the safety profile of mevrometostat plus enzalutamide and practical strategies for monitoring and dose modification.