Nivolumab Plus Ipilimumab Demonstrates Anti-Tumor Activity in Metastatic Castration-Resistant Prostate Cancer

Phase 2 data found that the combination of nivolumab plus ipilimumab demonstrated significant anti-tumor activity for patients with mCRPC.

The combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) demonstrated significant anti-tumor activity when treating patients with metastatic castration-resistant prostate cancer (mCRPC) and immunogenic signature, according to data presented at the virtual AACR Annual Meeting 2021.

The phase 2 NEPTUNES trial also demonstrated a safety profile that was consistent with previous research investigating this combination treatment regimen.

Median age of the patient population was 66.5 years (range, 50-70 years), with 51% of patients undergoing 3 or more prior systemic therapies and 89% of patients undergoing previous docetaxel treatment.

At the data cutoff point of January 4, 2021, 36 patients were included in the analysis, with a composite response rate of 28.6% (90% confidence limit [CL], 16.4-43.6). More, 22.9% of patients in cohort 1 experienced a prostate-specific antigen (PSA) response (90% CL, 11.9-37.5). Looking at both the radiological response and CTC response, 11.4% of patients experienced these responses, respectively (90% CL, 4.0-24.3).

“The composite response rate was 10 out of 35 patients, or 28.6%,” lead investigator Dr. Mark D. Linch, associate professor at University College London Cancer Institute, said in his presentation of the data. “This is numerically higher than other checkpoint inhibitor studies in prostate cancer, but it is insufficient to reject the null hypothesis that the composite response rate is less than 20%.”

Looking at secondary end points, median overall survival (OS) was recorded around 18 months, with a progression-free survival (PFS) of about 5 months.

In cohort 1, the safety profile was consistent with previously reported research on the combination treatment for mCRPC. The most common any grade adverse events (AEs) included diarrhea (57% of patients), rash (54%), fatigue (37%), increased liver enzymes (23%), and fever (20%).

Patients in cohort 1 experienced diarrhea as the most common grade 3 to 4 AE (17%). Serious AEs were reported in 20 of the 25 patients (57%), with diarrhea and pneumonitis reported as the most common serious AEs (13 and 4 events, respectively). No treatment-related deaths were reported.

“We hypothesized that men with defective DNA repair, defective mismatch repair or high inflammatory infiltrate will be more likely to respond to nivolumab plus ipilimumab,” explained Linch.

When examining responders using biomarkers, 4 out of the 5 patients with defective mismatch repair responded, with the fifth patient experiencing an unconfirmed partial response. More, 3 of the 4 patients with BRCA1/2 responded to the combination treatment.

Eligible patients for the research had mCRPC with confirmed ongoing antigen deprivation therapy, archival cancer tissue samples, 1 or more prior life-prolonging systemic therapy in the hormone-sensitive or castration-resistant setting, and a performance status of 0-1.

Patients in cohort 1 of the research received the combination of 1 mg/kg nivolumab plus 3 mg/kg ipilimumab for a 3-week cycle for a total of 4 cycles. After 6 weeks, patients received 480 mg nivolumab for a 4-week cycle up to 1 year.

The primary end point of the research was composite response rate, focusing on radiological response rate, PSA50 response rate, and the conversion of circulating tumor cells at 9 weeks. OS, radiological PFS, and the frequency of AEs were key secondary end points.

“We believe the further study of nivolumab and ipilimumab in biomarker-selected patients with metastatic castration-resistant prostate cancer is warranted,” explained Linch. “the rate of incomplete treatment was high, suggesting that alternative dosing schedules may be required.”


Linch MD, Wong YNS, Jones RJ, et al. Nivolumab (NIVO) and ipilimumab (IPI) treatment in prostate cancer with an immunogenic signature: cohort 1 of the NEPTUNES multi-centre, two-stage biomarker-selected Phase II trial. Presented at: AACR Annual Meeting 2021; April 10-15, 2021; Virtual. Abstract LB004.