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<p>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 (<i>n</i> = 73), nivolumab 1 mg /kg plus ipilimumab 3 mg /kg (<i>n</i> = 74), ipilimumab 3 mg /kg (<i>n</i> = 38), or cabazitaxel (<i>n</i> = 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, <i>n</i> = 12) identified a transcriptional signature, derived from the most highly expressed genes across cell types within select perivascular immune niches (comprising CD31<sup>+</sup> endothelial, CD14<sup>+</sup>HLA-DR<sup>+</sup> myeloid, and CD4<sup>+</sup> and CD8<sup>+</sup> 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.</p>

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Nivolumab plus ipilimumab for chemotherapy-refractory metastatic castration-resistant prostate cancer: results from the randomized portion of the phase 2 CheckMate 650 trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月8日

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  • 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

摘要

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.