Regulatory Decision Summary for Opdivo

Conditional authorization was primarily based on the results from an international, multicenter, single arm, open-label, phase 2 study in adult patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMRR) metastatic colorectal cancer (mCRC). In the study, 119 patients were treated with nivolumab in combination with ipilimumab. Among them, 82 patients received a prior treatment with fluoropyrimidine (5-FU)/capecitabine - containing regimens in combination with either oxaliplatin (Oxa) or irinotecan (Iri) (5FU-Oxa-Iri).

The primary objective of these studies was to determine if nivolumab in combination with ipilimumab demonstrates a clinical meaningful overall response rate (ORR) >30% based on historical controls. The blinded independent central review (BICR) assessed ORR was 59.7% in all treated subjects and was 56.1% in subjects with prior 5FU-Ora-Iri.

The adverse events reported in the clinical trial included adverse events, serious adverse events, drug-related adverse events, immune-mediated adverse events, and other events of special interest on the basis of previous experience with nivolumab in combination ipilimumab for the treatment of other cancer types. The overall safety profile in mCRC is similar to that of nivolumab combination therapy in other tumor types. No new safety concerns were identified.

Given the study design, there is residual uncertainty regarding the magnitude of the treatment effect with the combination therapy of nivolumab and ipilimumab. Nevertheless, the observed treatment benefit, in the context of a conditional authorization, demonstrated promising clinical evidence in terms of overall response rates in patients with MSI-H/dMMR mCRC. As a condition of authorization, the sponsor will be required to commit to file phase III trial data to confirm the efficacy of nivolumab combination therapy and the benefit/risk balance in patients with MSI-H/dMMR mCRC.