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mCRPC in focus

Transcript: Phase 1 trial of mevrometostat for CRPC

Last updated:4th Jul 2024
Published:4th Jul 2024

Dr Alexander Chehrazi-Raffle

Interview recorded June 2024. All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.

There was actually one poster that caught my eye as particularly promising. Abstract 5061 was a phase 1 trial of mevrometostat, which is a potent inhibitor of enhancer of zeste homolog 2, or EZH2 in mCRPC. So in this study, the investigators sought to assess safety, efficacy, and pharmacodynamics of mevrometostat in combination with enzalutamide, patients had to have progressed on an ARPI and prior taxane chemotherapy was permitted. Interestingly, of the 47 patients on this study, 35 had already received enzalutamide, meaning that the majority of patients were re-challenging with a medication that they had already progressed on. The remaining 12 patients had progressed on abiraterone.

Both combinations were overall very well tolerated, whether mevrometostat was given with enzalutamide, or when it was given with enzalutamide after abiraterone or previous enzalutamide, so the reason the study really stuck out to me is because median rPFS in the prior abiraterone arm was an impressive 17 months, and with prior enzalutamide was 12 months. When put into other, well into context of other clinical trials such as PSMA four, as I just mentioned, ARPI switch typically results in about six months of our rPFS benefit, meaning that the addition of mevrometostat may be adding up to an additional year of benefit. Acknowledging that this is only phase 1 data, this is quite impressive considering other studies in this space have yet to achieve such durable responses. Hopefully we see similarly encouraging data as the phase 3 studies are currently underway.

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