The addition of stereotactic body radiation therapy (SBRT) to nivolumab (Opdivo) plus ipilimumab (Yervoy) did not improve response rates or survival compared with the immunotherapy doublet alone in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC), according to findings from the randomized phase 2 CheckPRO trial (CA209-8TY; NCT05655715) published in Journal for ImmunoTherapy of Cancer.¹
Among evaluable patients, the confirmed prostate-specific antigen (PSA) response rate was 21.6% (95% CI, 9.8%-38.2%; n = 8 of 37) with SBRT plus nivolumab/ipilimumab (arm A) vs 20.5% (95% CI, 9.8%-35.3%; n = 9 of 44) with nivolumab/ipilimumab alone (arm B). The objective response rate (ORR) among patients with measurable disease was 16.7% (95% CI, 4.7%-37.4%; n = 4 of 24) in arm A and 22.2% (95% CI, 10.1%-39.2%; n = 8 of 36) in arm B, for an overall cohort ORR of 20%. Median overall survival (OS) was 10.2 months (95% CI, 7.1-15.2) in arm A and 9.2 months (95% CI, 7.1-14.4) in arm B.
"This single-center, investigator-initiated, randomized phase II trial successfully met the primary endpoint of PSA response for ≥8 patients in arms A and B, suggesting that the combination treatment with nivolumab and ipilimumab is beneficial for a subgroup of patients with mCRPC," the study authors wrote. "However, the addition of SBRT did not increase the response rates or survival outcomes in the evaluable nor the ITT patient population, indicating that our primary hypothesis was not supported."
CheckPRO Trial of Nivolumab/Ipilimumab ± SBRT in mCRPC: Key Findings
- Adding SBRT did not improve PSA response, ORR, PFS, or OS compared with nivolumab/ipilimumab alone; the trial's primary hypothesis of an SBRT-induced abscopal effect was not supported.
- The confirmed PSA response rate and ORR met the prespecified bar for the nivolumab/ipilimumab combination to be considered "promising" in both arms.
- Median OS was similar between arms A and B (10.2 vs 9.2 months), and patients without a PFS event within 6 months had substantially longer OS (27.6 vs 5.3 months).
How was CheckPRO designed?
CheckPRO was a single-center, investigator-initiated trial conducted at Herlev and Gentofte Hospital in Copenhagen, Denmark, that enrolled patients with histologically confirmed mCRPC who had received at least 2 prior lines of therapy in the metastatic setting, including at least 1 androgen receptor pathway inhibitor and 1 taxane-based chemotherapy regimen, a performance status of 0 or 1, no prior immunotherapy, and a metastatic lesion eligible for SBRT.1,2
Between November 2019 and January 2024, 91 patients were randomly assigned 1:1 to SBRT at 24 Gy in 3 fractions over 1 week plus nivolumab at 3 mg/kg, and ipilimumab at 1 mg/kg every 3 weeks for 4 cycles (arm A), or the same systemic regimen without SBRT (arm B); both arms continued nivolumab monotherapy at 480 mg every 4 weeks for up to 52 weeks.1
The co-primary end points were confirmed PSA response rate (PSA50) and ORR per Prostate Cancer Working Group 3 RECIST 1.1 criteria.
Eight patients in arm A and 2 in arm B did not receive the intended therapy because of clinical deterioration before treatment initiation, which was driven largely by the SBRT planning period in arm A, leaving 37 and 44 patients, respectively, evaluable for response, survival, and safety. Nearly all patients (97%) had received 3 or more prior lines of therapy, and more than 80% had bone metastases at baseline.
What biomarker and survival data were reported?
Patients with no progression-free survival (PFS) event within the first 6 months of treatment had a median OS beyond that landmark of 27.6 months (95% CI, 8.4-not reached) compared with 5.3 months (95% CI, 3.1-8.1) for those who progressed within 6 months. In exploratory biomarker analyses, patients with baseline lactate dehydrogenase (LDH) at or below the upper limit of normal had a median OS of 14.4 months vs 7.2 months for those with elevated LDH (P = .047); patients with baseline C-reactive protein (CRP) of 10 mg/L or lower had a median OS of 15.9 months vs 7.1 months for those with higher CRP (P < .0001); and patients with a neutrophil-to-lymphocyte ratio (NLR) below 5 had a median OS of 10.9 months vs 5.2 months for those with an NLR of 5 or higher. The median duration of response across the cohort was 5.5 months (95% CI, 1.5-22.3).
What were the safety data?
Any-grade adverse effects (AEs) occurred in all evaluable patients, with grade 3/4 events in 70.4% overall (67.6% in arm A and 72.7% in arm B). Grade 3/4 treatment-related AEs (TRAEs) occurred in 27 of 81 evaluable patients (33.3%), with no treatment-related deaths.
Treatment-related AEs (TRAEs) of any grade occurred in 92.6% of patients, and grade 3/4 TRAEs occurred in 33.3% (32.4% in arm A vs 34.1% in arm B), with no substantial differences between arms and no treatment-related deaths. The most common TRAEs of any grade were pruritus (39.5%), rash (35.8%), and dry skin (28.4%); the most common grade 3/4 TRAEs were colitis (9.9%) and diarrhea (6.2%). Ten patients discontinued therapy because of TRAEs, most commonly colitis. Serious AEs occurred in 61.7% of patients, and treatment-related serious AEs occurred in 34.6%.
The authors noted that heterogeneous SBRT delivery in arm A leaves open the question of whether SBRT can produce a genuine abscopal effect in mCRPC, and pointed to findings from the phase 2 NEPTUNES trial (NCT03061539), in which patients with an immunogenic tumor signature (mismatch repair deficiency, DNA damage repair alterations, or high inflammatory infiltrate) achieved a composite response rate of 32% with nivolumab plus ipilimumab, as support for further biomarker-driven patient selection in future ICI trials in mCRPC.
References
- Eefsen RL, Spindler NJ, Theile S, et al. 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. J Immunother Cancer. 2026;14(7):e014803. doi:10.1136/jitc-2026-014803
- Checkpoint inhibitors and SBRT for MCRPC (CheckPRO). ClinicalTrials.gov. Updated October 16, 2024. Accessed August 17, 2026. https://clinicaltrials.gov/study/NCT05655715
