625P Pembrolizumab (pembro) plus enzalutamide (enza) in patients with abiraterone acetate (abi)-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 Cohort C update

Pembo + enza (cohort C) has shown antitumor activity and acceptable safety in abi-pretreated patients (pts) with mCRPC in the phase I/II KEYNOTE-365 study (NCT02861573). Updated results from cohort C including time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression are reported. Pts who failed or became intolerant to abi after ≥4 wks of treatment in the prechemotherapy mCRPC state and who progressed within 6 mo of screening received pembro 200 mg IV Q3W + enza 160 mg/day orally. Primary end points: PSA response rate (decrease ≥50% from baseline, confirmed by a second value ≥3 wks later), ORR per RECIST v1.1 by blinded independent central review (BICR), and safety. Secondary end points: DCR, DOR; rPFS per PCWG-modified RECIST; OS, time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression. 102 of 103 enrolled pts were treated; 39% 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. In pts with measurable disease and ≥27 wks’ follow-up (n=25), confirmed ORR was 12% (2 CRs, 1 PR). For all pts, median rPFS was 6.1 mo (95% CI, 4.4-6.5) and median OS was 20.4 mo (95% CI, 15.5-NR). At 12 mo, rPFS rate was 24.6% and OS rate was 72.8% by Kaplan-Meier. Additional efficacy analyses are displayed in the table. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 40 pts (39%); 3 pts died of AEs (1 TRAE [cause unknown]). 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. The phase III KEYNOTE-641 study of this combination is ongoing (NCT03834493).Table: 625PDCR, n/N (%)aMeasurable disease8/25 (32)Nonmeasureable disease16/44 (36)Total24/69 (35)Median (range) DOR, moaNR (0.0+-24.4+)bMedian (95% CI), moTime to confirmed PSA progression3.5 (2.9-4.0)Time to symptomatic skeletal-related eventNR (18.2-NR)Event-free survival rate at 12 mo, %75.5Time to radiographic bone progression8.3 (6.7-10.8)Event-free survival rate at 12 mo, %32.9Time to radiographic soft-tissue progression15.2 (6.7-NR)Event-free survival rate at 12 mo, %56.8aWith ≥27 wks’ follow-up;b ‘+’ indicates ongoing responder;NR, not reached. Open table in a new tab