Prostate Cancer Coverage from Every Angle

AACR 2021: Nivolumab Plus Ipilimumab in Biomarker-Selected Patients With Metastatic Prostate Cancer

By: Susan Reckling
Posted: Tuesday, April 13, 2021

According to Mark D. Linch, PhD, of University College London, United Kingdom, and colleagues, the immunotherapy combination of nivolumab and ipilimumab demonstrated activity in biomarker-selected, pretreated patients with metastatic castration-resistant prostate cancer. Based on their findings from cohort 1 of the phase II NEPTUNES trial, the safety profile was consistent with the study’s dosing schedule. However, the rate of incomplete treatment suggests an alternative dosing schedule may be necessary. These results were presented during the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract LB004). In September 2020, accrual to expansion cohort 2 was initiated.

In cohort 1, 50 of 211 patients were considered positive for an immunogenic signature; the study authors proposed that such a preselected population might be more likely to respond to immunotherapy. Positivity was defined by at least one of the following methods: mismatch repair–deficient (MRD) immunohistochemistry; DNA damage repair–deficient excluding MRD detected by a targeted exome-sequencing assay; and high tumor-infiltrating lymphocytes (TILs) on multiplexed immunohistochemistry. Treatment consisted of nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg every 3 weeks for four doses, followed by nivolumab at 480 mg every 4 weeks.

At a median follow-up of 7.2 months, 35 of these 50 patients received the combination therapy. The overall composite response rate was 28.6%. Regarding the determinants of immunogenic signature positivity, four of the five patients with MRD responded to treatment, as did three of the four patients with BRCA1/2 mutation; two of nine patients with high TILs responded to therapy. The median duration of response was 4.9 months (range, 1.8–19.7 months). As for toxicity, nearly half of the patients (17 of 35) experienced a grade 3 or 4 treatment-related adverse event.

Disclosure: Dr. Linch reported relationships with BioNTech, Pfizer, Bristol Myers Squibb, AstraZeneca, Shionogi, Astellas, MSD, Janssen, and Roche. For disclosures of the other study authors, visit

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