Pembrolizumab (PD-1) + Lenvatinib (VEGFR/FGFR multikinase) posts 36% ORR in docetaxel-pretreated mCRPC (KEYNOTE-365)

Pembrolizumab is an anti–PD-1 monoclonal antibody, and lenvatinib is an oral anti-angiogenic multikinase inhibitor (VEGFR/FGFR/PDGFRα/RET/KIT); the combination was tested in KEYNOTE-365 Cohort E (Phase 1b/2) in docetaxel-pretreated metastatic castration-resistant prostate cancer (ECOG 0–1; n=39; median follow-up 9.7 months). Confirmed PSA response rate was 34% (95% CI 20–51), and in RECIST-measurable disease, the confirmed ORR was 36% (95% CI 18–57)—numerically higher than historical post-docetaxel abiraterone + prednisone PSA response ~29.5% in COU-AA-301, though cross-trial comparisons are fragile and this cohort is small. Safety was intensive: treatment-related AEs occurred in 92%, with grade 3–5 treatment-related AEs in 62% (notably higher than typical post-docetaxel ARSI tolerability), and there were 2 non–treatment-related deaths (acute kidney injury; unspecified); trial ID: NCT02861573.