KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.
Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines. Patients with RECIST-measurable disease were enrolled in C4, and patients with bone-only or bone-predominant disease were enrolled in C5. All patients received pembrolizumab 200 mg every 3 weeks for ≤35 cycles with ongoing enzalutamide until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review in C4. Secondary end points included disease control rate (DCR), overall survival, and safety in each cohort and both cohorts combined.
A total of 126 patients were treated (C4, n = 81; C5, n = 45). Median age was 72 years (range 43-92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1-21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7-64.3%) in C4 and 51.1% (95% CI 35.8-66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0-22.6) in C4 and 20.8 months (95% CI 14.1-28.9) in C5. Grade ≥3 treatment-related adverse events occurred in 35 patients (27.8%); 2 patients in C4 died from immune-related adverse events (myasthenic syndrome and Guillain-Barré syndrome).
The addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile.
ClinicalTrials.gov, NCT02787005.
Prostate cancer and prostatic diseases. 2024 Aug 12 [Epub ahead of print]
Julie N Graff, Christopher J Hoimes, Winald R Gerritsen, Ulka N Vaishampayan, Tony Elliott, Clara Hwang, Albert J Ten Tije, Aurelius Omlin, Raymond S McDermott, Yves Fradet, Scott T Tagawa, Deepak Kilari, Cristiano Ferrario, Hiroji Uemura, Robert J Jones, Satoshi Fukasawa, Avivit Peer, Cuizhen Niu, Christian H Poehlein, Ping Qiu, Leah Suttner, Ronald de Wit, Charles Schloss, Johann S de Bono, Emmanuel S Antonarakis
Oregon Health and Science University, Portland, OR, USA. ., Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA., Radboud University Medical Center, Nijmegen, Netherlands., University of Michigan and Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA., NHS Lothian, Edinburgh, UK., Henry Ford Health System, Detroit, MI, USA., Amphia Hospital, Breda, Netherlands., Onkozentrum Zurich, University of Zurich and Tumorzentrum Hirslanden Zurich, Zurich, Switzerland., Tallaght University Hospital, Dublin, Ireland., CHU de Québec-Université Laval, Québec City, QC, Canada., Weill Cornell Medical College, New York, NY, USA., Medical College of Wisconsin, Milwaukee, WI, USA., Jewish General Hospital, Montreal, QC, Canada., Yokohama City University Medical Center, Yokohama, Japan., University of Glasgow, Glasgow, UK., Chiba Cancer Center, Chiba, Japan., Rambam Health Care Campus, Haifa, Israel., MSD China, Beijing, China., Merck & Co., Inc., Rahway, NJ, USA., Erasmus University Medical Center, Rotterdam, Netherlands., The Royal Marsden Hospital NHS Foundation Trust and the Institute of Cancer Research, London, UK., The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.