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
Vaishampayan UN, Elliott T, Omlin AG, Graff JN, Hoimes CJ, Tagawa ST, Hwang C, Kilari D, Tije AJT, McDermott RS, Gerritsen WR, Wu H, Kim J, Schloss C, de Bono JS, and Antonarakis ES. 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. Annals of Oncology 2020; 31:S1330.
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.