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Randomized phase II trial of nivolumab and ipilimumab with or without stereotactic body radiation therapy in patients with metastatic castration-resistant prostate cancer: the CheckPRO, CA209-8TY trial

In brief

SBRT adds no benefit to nivolumab and ipilimumab in metastatic prostate cancer

In a randomized phase II trial of 81 men with heavily pretreated metastatic castration-resistant prostate cancer, PSA response occurred in about 21% of patients whether or not stereotactic body radiation was added, and median overall survival was only a month longer with SBRT (10.2 vs 9.2 months). Grade 3-4 toxicities affected one-third of participants, indicating that radiation did not improve outcomes and biomarker work is needed to pinpoint responders.

Journal
Journal for immunotherapy of cancer (Q1)
Published
23 July 2026
Study design
Phase 2 randomized trial (exploratory)
Evidence level
Level 2, Moderate (CEBM 2b)
Authors
Rikke Løvendahl Eefsen, Nicklas Juel Spindler, Susann Theile, Gina Al-Farra, Helle W Hendel, Torben Lorentzen, et al.
PMID
42493213
DOI
10.1136/jitc-2026-014803

Why clinicians should know about it

Abstract

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is among the leading causes of cancer-related mortality in men worldwide. Treatment options for mCRPC typically include chemotherapy and androgen receptor pathway inhibitors. Immune checkpoint inhibitors (ICIs) have demonstrated a limited effect in mCRPC. We hypothesized that the addition of stereotactic body radiation therapy (SBRT) could enhance immune responses and improve treatment outcomes. METHODS: Patients with mCRPC who had received at least two prior lines of therapy were randomized 1:1 to receive SBRT with nivolumab and ipilimumab (arm A) or nivolumab and ipilimumab (arm B). The dual primary endpoints in the study were prostate-specific antigen (PSA) response rate and objective response rate (ORR). Secondary endpoints included overall survival (OS), PSA, radiologic progression-free survival, and toxicity. RESULTS: We enrolled 91 patients, and 81 patients received at least one treatment with ICIs and were eligible for evaluation of the efficacy and safety endpoints. Of the evaluable patient population, the confirmed PSA response rate was 21.6% (95% CI 9.8% to 38.2%) in arm A, and 20.5% (95% CI 9.8% to 35.3%) in arm B. ORR was 16.7% (95% CI 4.7% to 37.4%) and 22.2% (95% CI 10.1% to 39.2%) in arms A and B, respectively. Median OS was 10.2 months (95% CI 7.1 to 15.2) in arm A and 9.2 months (95% CI 7.1 to 14.4) in arm B. Treatment-related adverse events grade 3-4 were observed in 27 patients (33.3%). CONCLUSIONS: The addition of SBRT to nivolumab and ipilimumab did not improve outcomes; however, a fraction of the patients had a response to the treatment combination of nivolumab and ipilimumab. Explorative translational research is needed to identify possible biomarkers of response to immunotherapy with ICIs in mCRPC. TRIAL REGISTRATION NUMBERS: European Union Clinical Trial Registry (https://www.clinicaltrialsregister.eu) EudraCT number: 2018-003461-34 and on https://clinicaltrials.gov (NCT05655715).

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.