We report on the randomized portion of the phase 2, open-label CheckMate 650 trial (NCT02985957), in which docetaxel-experienced, biologically male patients with chemotherapy-refractory metastatic castration-resistant prostate cancer were randomized 2:2:1:2 to nivolumab 3 mg /kg plus ipilimumab 1 mg /kg (n = 73), nivolumab 1 mg /kg plus ipilimumab 3 mg /kg (n = 74), ipilimumab 3 mg /kg (n = 38), or cabazitaxel (n = 74). Primary endpoints were objective response rate and radiographic progression-free survival; key secondary endpoints included overall survival, prostate-specific antigen response rate, and safety. This portion of CheckMate 650 was not designed to statistically compare between cohorts. Respectively, objective response rates (95% CI) were 9.3% (2.6-22.1), 19.5% (8.8-34.9), 4.5% (0.1-22.8), and 12.2% (4.1-26.2), and median radiographic progression-free survival (95% CI) was 3.9 (2.2-7.6), 4.2 (3.3-5.6), 3.5 (2.1-5.8), and 7.9 (5.6-9.3) months. Respective incidence of grade ≥3 treatment-related adverse events was 28.8%, 30.1%, 18.4%, and 34.7%. Preliminary post hoc biomarker analyses in patients who received treatment with any immunotherapy regimen (i.e., treated with either of the nivolumab plus ipilimumab regimens or with ipilimumab alone, n = 12) identified a transcriptional signature, derived from the most highly expressed genes across cell types within select perivascular immune niches (comprising CD31+ endothelial, CD14+HLA-DR+ myeloid, and CD4+ and CD8+ T cells), which was associated with prolonged overall survival. These results provide further evidence of antitumor activity with nivolumab plus ipilimumab in select patients with metastatic castration-resistant prostate cancer and nominate a candidate prognostic biomarker that warrants confirmation in future prospective clinical trials.
Nature communications. 2026 May 08 [Epub ahead of print]
Padmanee Sharma, Michael Krainer, Fred Saad, Daniel Castellano, Jens Bedke, Mariusz Kwiatkowski, Akash Patnaik, Giuseppe Procopio, Paweł Wiechno, Samith Kochuparambil, Christian Thomas, José Ángel Arranz Arija, Steven L McCune, Steinbjørn Hansen, Gedske Daugaard, Juan Ignacio Delgado Mingorance, Craig Kukard, Sumit K Subudhi, Sreyashi Basu, Sonali Jindal, Bilal A Siddiqui, Ana Lako, Saurabh Gupta, Viktor Fedorov, Neha P Amin, Arancha Campos, Yumeng Wang, Justin M David, Russell K Pachynski
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ., Department of Medical Oncology, Clinic for Internal Medicine 1, Medical University Vienna, Vienna, Austria., Department of Urology, Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal, QC, Canada., Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., Department of Urology, Eberhard Karls University of Tübingen, Tübingen, Germany., Department of Chemotherapy, Szpital Wojewódzki im. Mikołaja Kopernika w Koszalinie, Koszalin, Poland., Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA., Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy., Maria Skłodowska-Curie Memorial Cancer Center, Warsaw, Poland., Minnesota Oncology, Minneapolis, MN, USA., Department of Urology, Technische Universität Dresden, Dresden, Germany., Hospital General Universitario Gregorio Marañón, Madrid, Spain., Northwest Georgia Oncology Centers Wellstar, Marietta, GA, USA., Odense University Hospital, Odense, Denmark., University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark., Hospital Universitario Infanta Cristina, Badajoz, Spain., Central Coast Cancer Centre, University of Newcastle, Gosford, NSW, Australia., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Bristol Myers Squibb, Princeton, NJ, USA., Division of Oncology, Washington University School of Medicine, St Louis, MO, USA.