ASCO: Results of KEYNOTE-365

Pembrolizumab (pembro) plus enzalutamide (enza) in patients (pts) with abiraterone acetate (abi)-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort C efficacy, safety, and biomarker results

Abstract Number : 5545

Abstract Type : Poster Session

Indication : Metastatic Castration Sensitive Prostate Cancer

Intervention : Pembrolizumab (pembro) plus enzalutamide (enza)

Company : Merck Sharp & Dohme Corp.

Technology : Monoclonal antibody


Of 103 enrolled pts, 102 were treated; 39% of treated pts had measurable disease. Median (range) time from enrollment to data cutoff was 19.1 mo (1.1-28.8) for all pts and 21.4 mo (15.1-28.8) for pts with $27 wks’ follow-up (n=69). Confirmed PSA response rate was 22% in 101 pts with a baseline PSA assessment. Median time to PSA progression was 3.5 mo (95% CI, 2.9-4.0). In pts with measurable disease and $27 wks’ follow-up (n=25), confirmed ORR was 12% (2 CRs, 1 PR) and DCR was 32%. Median DOR was not reached (range, 0.0+ to 24.4+ mo); 2 pts had a response for $6 mo. In all pts, median (95% CI) rPFS was 6.1 mo (4.4-6.5) and median OS was 20.4 mo (15.5-NR). At 6 mo, rPFS rate was 55.1% and OS rate was 88.2%. Treatment-related AEs occurred in 92 pts (90%); most frequent ($20%) were fatigue (38%), nausea (22%), and rash (20%). Grade 3-5 treatment-related AEs occurred in 40 pts (39%). Three pts died of AEs (1 AE was treatment related [cause unknown]). Of all pts, 29% had PD-L1+ tumors (combined positive score $1). Of 51 pts with AR-v7 data, 13.7% were AR-v7+ and 86.3% were AR-v72. GEP was not significantly associated with

ORR or PSA response.


Pembro + enza continued to show activity in pts with abi-pretreated mCRPC. Safety of the combination was consistent with the known profiles of pembro and enza. A phase III study of this combination is ongoing (KEYNOTE-641, NCT03834493).


Pembrolizumab plus enzalutamide showed promising activity and acceptable tolerability in in patients with abiraterone acetate pretreated mCRPC, supporting further evaluation in a phase 3 study.

Refer to Metastatic Castration Sensitive Prostate Cancer Market report for detailed Insights.