Administration of nivolumab plus ipilimumab: Infusion of the fixed-ratio combination versus sequential infusions in two randomized controlled trials of metastatic melanoma (CheckMate 742) and renal cell carcinoma (CheckMate 800).

Abstract

Immune checkpoint inhibitors can be coadministered as a fixed-ratio combination (FRC) or administered as sequential infusions (ASI). Two randomized, open-label trials compared nivolumab + ipilimumab as a FRC versus ASI in patients with melanoma or renal cell carcinoma. CheckMate 742 was a Phase 3b study in patients with advanced or metastatic melanoma who received nivolumab 1 mg/kg and ipilimumab 3 mg/kg either concurrently as an FRC or sequentially as ASI every 3 weeks. CheckMate 800 was a Phase 2 study in patients with advanced or metastatic renal cell carcinoma who received nivolumab 3 mg/kg and ipilimumab 1 mg/kg either concurrently as an FRC or sequentially as ASI every 3 weeks. The primary endpoint was the incidence of adverse events (AEs) in the Broad Scope Medical Dictionary for Regulatory Activities (MedDRA) Anaphylactic Reaction Standardized MedDRA Queries (SMQ) occurring within 2 days after dosing. Secondary endpoints included incidence of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ. There was no clinically relevant difference in safety between FRC and ASI as measured by the primary endpoint in either study; odds ratio (95% CI) of 0.87 (0.30-2.49) and 1.0 (0.30-3.39) for CheckMate 742 and CheckMate 800, respectively. No AEs were reported in the Narrow Scope MedDRA Anaphylactic Reaction SMQ in either study. One death from drug toxicity occurred in CheckMate 742. Both studies met their primary endpoint. The safety profiles of nivolumab + ipilimumab as FRC or ASI were acceptable and manageable. NCT02905266 and NCT03029780 for CheckMate 742 and CheckMate 800, respectively.