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

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Conference Proceeding

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Annals of Oncology


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 pts who 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 review in C4; DOR was 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.

Conclusions: After enza resistance, pembro + enza showed antitumor activity and manageable safety for RECIST-measurable and bone-predominant mCRPC. Pembro + enza is being evaluated in the ongoing phase III KEYNOTE-641 trial.


(NCT03834493). Clinical trial identification: NCT02787005, June 1, 2016.





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