1603P - Updated safety and efficacy of tazemetostat (TAZ) plus enzalutamide (ENZ) in patients with metastatic castration-resistant prostate cancer (mCRPC)

Background

TAZ is a first-in-class, selective oral inhibitor of EZH2. Preclinically, EZH2 inhibition can reverse lineage plasticity and resistance to next-generation hormonal agents in mCRPC. Here, we present updated results from the phase 1b/2 EZH-1101 study (NCT04179864) evaluating TAZ+ENZ in patients with progressive mCRPC.

Methods

Patients with chemotherapy-naïve mCRPC who had progressed on abiraterone were randomized to receive TAZ 1200 mg BID plus ENZ 160 mg QD or ENZ 160 mg alone QD. Primary endpoint was radiographic progression-free survival (rPFS) by blinded central review (BCR). Secondary endpoints included objective response rate (ORR) by BCR, and safety.

Results

As of 30 September 2023, 81 patients were randomised to the phase 2 part of the study (TAZ+ENZ n=41; ENZ n=40). Median ages were 72.0 and 68.5 years for TAZ+ENZ and ENZ, respectively, with most patients having ECOG PS of 0 (56.1% and 55.0%). Median rPFS by BCR was 16.6 and 13.8 months for TAZ+ENZ and ENZ, respectively (p=0.3704) (Table). Of patients with measurable baseline soft tissue disease, ORR by BCR for TAZ+ENZ was 8.3% and 16.7% for ENZ. Best overall response (BOR) for TAZ+ENZ was 1 patient with a partial response (PR; 8.3%) and 8 patients with stable disease (SD; 66.7%); BOR by BCR for ENZ was 1 complete response (8.3%), 1 PR (8.3%) and 6 patients with SD (50.0%). The most frequent any-grade treatment-emergent adverse events (TEAEs) for TAZ+ENZ were fatigue (65.9%) and nausea (46.3%); most frequent for ENZ were fatigue (30.0%), back pain (22.5%), and decreased appetite (22.5%). Grade ≥3 TEAEs were reported by 46.3% and 42.5% for TAZ+ENZ and ENZ, respectively. Table: 1603P

Summary of efficacy endpoints

*Patients with baseline measurable soft tissue disease; ^†1 patient NE due to withdrawing from study.CI, confidence interval; HR, hazard ratio; NE, not evaluable.

Conclusions

Combination therapy with TAZ+ENZ extended median rPFS by 2.8 months, although this was not statistically significant. No significant difference was identified for ORR. The safety profile of TAZ+ENZ was consistent with data from previously reported studies.

Clinical trial identification

NCT04179864.

Editorial acknowledgement

The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment related to the development of the abstract. Amber Wood, PhD, of Nucleus Global provided writing and editorial support, which was contracted and funded by Epizyme, an Ipsen company.

Legal entity responsible for the study

Ipsen Bioscience, Inc.

Funding

Epizyme, an Ipsen company.

Disclosure

W. Abida: Financial Interests, Personal, Speaker, Consultant, Advisor, Speaker: Roche, Medscape, Clinical Education Alliance, Aptitude Health, MJH Life Sciences, Touch IME, Pfizer, theMedNet; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting: Clovis Oncology, Janssen, ORIC Pharmaceuticals, Daiichi Sankyo, AstraZeneca, Pfizer, Laekna Therapeutics, MOMA Therapeutics; Non-Financial Interests, Personal, Advisory Role: Nuvation Bio and Endeavor BioMedicines. L.J. Appleman: Financial Interests, Personal, Research Grant: Amgen Inc. M. Taplin: Financial Interests, Personal, Advisory Role: Arvinas, Bayer, and Janssen Pharmaceuticals Inc. Á. Juárez: Financial Interests, Personal, Advisory Board: Astellas, Bayer and Janssen; Financial Interests, Personal, Principal Investigator: Bayer and Janssen; Financial Interests, Personal and Institutional, Research Funding: Janssen. L. Zhang, Y. Chen, N. Gupta: Financial Interests, Personal, Full or part-time Employment: Ipsen. D. Saltzstein: Financial Interests, Personal, Advisory Role: Astellas Pharma Inc., Janssen Pharmaceuticals, and Medivation.