Pembrolizumab has shown manageable safety and modest antitumor activity when used as a single agent in participants with metastatic castration-resistant prostate cancer (mCRPC). Preclinical evidence suggests that lenvatinib, a vascular endothelial growth factor-targeted agent, inhibits angiogenesis and cell migration in prostate cancer. Safety and efficacy of pembrolizumab plus lenvatinib in participants with docetaxel-pretreated mCRPC were evaluated in cohort E of the phase 1b/2 KEYNOTE-365 study. Eligible adults with confirmed mCRPC, Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 0 or 1, and prior docetaxel treatment for mCRPC received pembrolizumab 200 mg intravenously every 3 wk, for ≤35 cycles, plus oral lenvatinib 20 mg daily, continuously from day 1 of cycle 1, unless specific discontinuation criteria were met. Primary endpoints were prostate-specific antigen (PSA) response rate; objective response rate (ORR), per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST) v1.1, by blinded independent central review; and safety. A total of 39 participants received treatment, with a median follow-up of 9.7 mo (interquartile range, 8.5-11.3). Confirmed PSA response rate was 34% (95% confidence interval [CI], 20-51). ORR for participants with RECIST-measurable disease was 36% (95% CI, 18-57). Treatment-related adverse events (AEs) of any grade occurred in 92% of participants and grade 3-5 treatment-related AEs occurred in 62% of participants. Two participants died of non-treatment-related AEs (acute kidney injury and unspecified death). Clinical trial registry: NCT02861573.
European urology oncology. 2026 May 02 [Epub ahead of print]
Marinela Augustin, Brigitte Laguerre, Capucine Baldini, Ahmed H Zedan, Enrique Gonzalez-Billalabeitia, Peter C Fong, Ruslan Zukov, Peter Hammerer, Mark Prentice, Neal Shore, Andrea Necchi, Tilman Todenhöfer, Elizabeth R Kessler, Fatih Kose, Howard Gurney, Begona P Valderrama, Pengfei Zhu, Kentaro Imai, Yingjie Liu, Ray McDermott
Department of Hematology and Oncology, Klinikum Nuernberg, Paracelsus Medical University, Campus Nuernberg, Nuernberg, Germany., Centre Eugène Marquis, Rennes, France., Drug Development Department (DITEP) Gustave Roussy, Villejuif, France., Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark., Hospital Universitario 12 de Octubre, Madrid, Spain., Auckland City Hospital and University of Auckland, Auckland, New Zealand., V. F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation., Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany., Royal Free Hospital, London, United Kingdom., Carolina Urologic Research Center, Myrtle Beach, SC, USA., Vita-Salute San Raffaele University, Milan, Italy; IRCCS San Raffaele Hospital, Milan, Italy., Studienpraxis Urologie, Nürtingen, Germany., University of Colorado Cancer Center, Anschutz Medical Campus, Aurora, CO, USA., Başkent University, Ankara, Turkey., Maquarie University, Sydney, NSW, Australia., Hospital Universitario Virgen del Rocío, Seville, Spain., MSD China, Shanghai, China., Merck & Co., Inc., Rahway, NJ, USA., St Vincent's University Hospital, Cancer Trials Ireland, Dublin, Ireland. Electronic address: .