Multinational phase 2 trial of nivolumab plus ipilimumab for chemotherapy-refractory mCRPC: results from CheckMate 650

In the randomized portion of the multinational phase 2 CheckMate 650 trial, docetaxel-experienced patients with chemotherapy-refractory metastatic castration-resistant prostate cancer (mCRPC) 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 (ORR) and radiographic progression-free survival (rPFS). This portion of CheckMate 650 was not designed to statistically compare between cohorts. Respectively, ORRs were 9.3% (95% CI 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 rPFS were 3.9 months (95% CI 2.2-7.6), 4.2 months (3.3-5.6), 3.5 months (2.1-5.8), and 7.9 months (5.6-9.3). Respective incidences of grade ≥ 3 treatment-related adverse events were 28.8%, 30.1%, 18.4%, and 34.7%. Preliminary post hoc biomarker analyses in patients who received any immunotherapy regimen identified a transcriptional signature, derived from the most highly expressed genes across cell types within select perivascular immune niches, which was associated with prolonged overall survival. The authors conclude that these results provide further evidence of antitumor activity with nivolumab plus ipilimumab in select patients with mCRPC.