The combination of nivolumab and ipilimumab demonstrated clinical activity in patients with metastatic castration-resistant prostate cancer (mCRPC), but adding stereotactic body radiation therapy (SBRT) to this immunotherapy regimen failed to improve treatment outcomes, according to results from the phase 2 CheckPRO trial presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
Trial Design and Patient Population
The randomized phase 2 CheckPRO trial (NCT05655715) enrolled 90 patients with mCRPC who were randomly assigned 1:1 to receive either nivolumab plus ipilimumab with SBRT (arm A) or nivolumab plus ipilimumab alone (arm B). In arm A, patients received SBRT at 8 Gy administered three times to a metastatic lesion, along with nivolumab at 3 mg/kg intravenously every 3 weeks and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 cycles. Arm B patients received the same immunotherapy regimen without radiation.
Following the initial treatment phase, all patients continued with nivolumab 480 mg intravenously every 4 weeks for up to 52 weeks, with re-induction therapy available for those experiencing progressive disease.
The study population consisted of heavily pretreated patients, with 100% of arm A patients and 93.2% of arm B patients having received three or more prior lines of therapy. The median age was 72 years in arm A and 73 years in arm B.
Primary Efficacy Results
The trial's co-primary endpoints were prostate-specific antigen (PSA) response rate and objective response rate (ORR). The PSA response rate, defined as more than 50% PSA decline confirmed four weeks later, was 21.6% (95% CI, 9.8%-38.2%) in the SBRT combination arm compared to 20.5% (95% CI, 9.8%-35.3%) in the immunotherapy-only arm.
The ORR per Prostate Cancer Working Group RECIST 1.1 criteria was 16.7% (95% CI, 4.7%-37.4%) for the combination arm versus 22.2% (95% CI, 10.1%-39.2%) for immunotherapy alone, showing no benefit from the addition of radiation therapy.
Survival Outcomes
Secondary endpoints revealed similar survival outcomes between the two treatment arms. The median PSA progression-free survival (PFS) was 2.6 months (95% CI, 1.9-3.8) for the SBRT combination arm and 2.5 months (95% CI, 1.9-3.0) for immunotherapy alone. Radiographic PFS was 2.1 months (95% CI, 1.9-3.8) versus 1.9 months (95% CI, 1.8-2.5), respectively.
Overall survival showed no significant difference, with 10.2 months (95% CI, 7.1-14.1) in the combination arm compared to 9.2 months (95% CI, 7.1-14.1) in the immunotherapy-only arm.
Safety Profile
The safety analysis included 81 evaluable patients, revealing that adverse events of any grade occurred in 100% of patients, with 70.4% experiencing grade 3/4 events. Treatment-related adverse events (TRAEs) of any grade were observed in 92.6% of patients, with 33.3% experiencing grade 3/4 TRAEs.
The most common TRAEs of any grade included pruritus (39.5%), rash (35.8%), liver transaminase increase (22.2%), hypothyroidism (19.8%), and diarrhea (19.8%). Grade 3/4 adverse events included colitis (9.9%), diarrhea (6.2%), hepatitis (4.9%), pneumonitis (3.7%), and hyperglycemia (2.5%). Treatment-related serious adverse events occurred in 34.6% of the combination arm versus 30.9% of the immunotherapy-only arm.
Clinical Implications
"Responses were demonstrated in a subgroup of patients with mCRPC treated with [immune checkpoint inhibitors (ICI)]," said Rikke Eefsen, MD, PhD, a medical oncologist from Herlev Gentofte Hospital in Copenhagen, Denmark, who presented the findings. "The addition of SBRT was safe, but it did not improve treatment outcomes."
The results suggest that while the nivolumab-ipilimumab combination shows activity in a subset of mCRPC patients, the addition of SBRT does not enhance the therapeutic benefit of this immunotherapy approach. The study underscores the challenge of identifying optimal combination strategies for mCRPC, particularly in heavily pretreated patients.
Dr. Eefsen noted that "further analyses are ongoing to identify patients with mCRPC, who most likely respond to ICI," highlighting the need for biomarker development to better select patients who may benefit from immune checkpoint inhibitor therapy in this challenging disease setting.
