Phase II study of pembrolizumab (pembro) plus enzalutamide for enzalutamide (enza)-resistant metastatic castration-resistant prostate cancer (mCRPC): Cohorts (C) 4 and 5 update from KEYNOTE-199

Abstract

Background: Chemotherapy-naive patients (pts) with mCRPC who had disease progression with enza were enrolled in C4 and C5 of the multicohort phase II KEYNOTE- 199 study (NCT02787005). Methods: Pts who did or did not previously take abiraterone acetate were eligible if they developed resistance to enza after prior response. Cohorts were composed of ptswho had RECIST-measurable (C4) or bone-predominant nonmeasurable (C5) disease. Pts received pembro 200 mg Q3W for up to 35 cycles + enza QD until progression, toxicity, or withdrawal. The primary end point was ORR per RECIST v1.1 by blinded independent central reviewin C4; DORwas also analyzed. Secondary end points (both cohorts)were DCR, rPFS, OS, time to cytotoxic chemotherapy, time to new anticancer therapy, and safety. Results: A total of 126 pts (C4, 81; C5, 45) were treated. Median (range) time from enrollment to data cutoff was 15 mo (7-21) and 19 mo (7-21) in C4 and C5, respectively. In C4, ORR (95% CI) was 12% (6-22) (2 CRs, 8 PRs) and median (range) DOR was 6.3 mo (2.5+ to 13.4); 4 responders (73% by Kaplan-Meier estimation) had a response 6 mo (Table). Median time to cytotoxic chemotherapy was 11.1 and 11.3 mo in C4 and C5, and time to PSA progression was 4.2 mo in both cohorts (Table). A total of 26% and 24% of pts in C4 and C5, respectively, experienced grade 3 treatment-related adverse events (TRAEs). Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any-grade/grade 3 or 4 rash (33%/6%), regardless of treatment relatedness, was higher than previously reported for individual agents but manageable with standard-of-care treatments.