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

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Conference Proceeding

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Annals of Oncology


Background: We present results including time to cytotoxic chemotherapy and time to new anticancer therapy from the multicohort phase 2 study KEYNOTE-199 (NCT02787005) in chemotherapy-naive patients (pts) with mCRPC treated with pembrolizumab (pembro) + enzalutamide (enza) after progression on enza and who had RECIST-measurable (C4) or bone-predominant nonmeasurable (C5) disease. Methods: Pts with or without prior abiraterone were eligible if they developed resistance to enza following prior response. Pts continued on enza and received pembro 200 mg IV Q3W for up to 2 y or until progression, toxicity, or withdrawal. End points: ORR per RECIST v1.1 (C4) by blinded independent central review (primary), DOR (C4), DCR, rPFS per PCWG3-modified RECIST, OS, time to cytotoxic chemotherapy, time to new anticancer therapy, and safety. Results: 126 pts (C4, 81; C5, 45) were treated. Median (range) PSA was 31 ng/mL (0.4-1667) in C4 and 19 ng/mL (1-1750) in C5. Median (range) time from enrollment to data cut off was 15 mo (7-21) in C4 and 19 mo (7-21) in C5. 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. Efficacy analyses are displayed in the table. Grade ≥3 treatment-related AEs occurred in 26% of pts in C4 and 24% in C5. Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any grade/grade 3-4 rash (regardless of treatment relatedness) was higher than previously reported for individual agents (33%/6%) but manageable with standard of care treatments. [Formula presented] Conclusions: Pembro + enza after enza resistance had manageable safety and showed antitumor activity for RECIST-measurable and bone-predominant mCRPC. This combination is being evaluated in the ongoing KEYNOTE-641 phase III trial (NCT03834493). Clinical trial identification: NCT02787005.



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