CA209-8TY trial, a randomized phase 2 trial of nivolumab and ipilimumab with or without stereotactic body radiation therapy in metastatic castration-resistant prostate cancer.

5018 Background: Metastatic castration-resistant prostate cancer (mCRPC) is among the leading causes of cancer related mortality in men worldwide. Treatment options include chemotherapy and androgen receptor pathway inhibitors (ARPIs). Prostate cancer is considered an immunosuppressive tumor. As of today, immune checkpoint inhibitors (ICIs) have not demonstrated effect in patients with mCRPC. The use of stereotactic body radiation therapy (SBRT) may increase the expression of tumor associated antigens and enhance potential immune responses following systemic therapy. Methods: Patients with mCRPC, who had previously progressed on at least one taxane regimen and one ARPI, were screened for the trial. Eligible Patients were randomized to receive either ipilimumab 1mg/kg and nivolumab 3mg/kg every 4 weeks for the first 12 weeks followed by nivolumab monotherapy 480mg every 4 weeks for up to 52 weeks (arm B), or the same ICI with SBRT of a metastasis, 24Gy in 3 fractions (arm A). The co-primary endpoints were prostate specific antigen (PSA) response rate, defined as a ≥50% decline in PSA compared to baseline, confirmed after ≥4 weeks, and objective response rate (ORR) according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Prostate Cancer Working Group (PCWG) 3. Secondary endpoints included overall survival (OS), radiologic progression free survival (rPFS), and toxicity. Results: Between November 2019 and January 2024, 91 patients were randomized in the CheckPRO trial (NCT 05655715). A total of 81 patients received at least one treatment cycle and were eligible for evaluation. The confirmed PSA response rate was 21.6% in arm A and 20.5% in arm B. ORR was 16.7% (95% CI [4.7-37.4] %) and 22.2% (95% CI 10.1-39.2) in arm A and B, respectively. Median OS was 10.2 months (95% CI [7.1-14.1] %) in arm A and 9.2 months (95% CI [7.1-14.1] %) in arm B. rPFS was 2.1 months and 1.9 months in arm A and B, respectively. Serious adverse events related to ICIs occurred in 29.7% of patients in arm A and 31.8% in arm B. Conclusions: Objective responses were demonstrated in patients with mCRPC treated with combination ICI, however PFS was short and treatment-related toxicity significant. While the addition of SBRT was safe, it did not improve treatment outcomes in this study. Further analyses are ongoing to identify patients with mCRPC, who are most likely to respond to ICI. Clinical trial information: NCT05655715 .