OBJECTIVES: To conduct a NMA of available 1L IO treatments in metastatic melanoma to assess the relative efficacy and safety of fixed-dose combination nivolumab+relatimab (NIVO+RELA).

METHODS: A systematic literature review (SLR) informed a Bayesian NMA evaluating overall survival (OS) and progression-free survival (PFS) using constant hazard ratio (HR) and time-varying HRs. Safety analyses were conducted for all-cause and treatment-related grade 3/4 adverse events (AEs). IO comparators were NIVO 1 mg/kg + ipilimumab 3mg/kg (NIVO1+IPI3), pembrolizumab (PEM), and NIVO monotherapy. Analyses were conducted for the all-comers and PD-L1<1% populations separately. All results were from fixed effect analyses and are presented as HRs (for OS/PFS) or odds ratios (OR; for safety) with associated 95% credible intervals (CrI).

RESULTS: In the constant HR analysis, NIVO+RELA was similar to NIVO1+IPI3 in terms of both PFS (HR 1.03 [0.79, 1.34]) and OS (HR 0.96 [0.72-1.27]). For the comparison versus PEM, the point estimate favored NIVO+RELA, although the upper bound of the CrI crossed 1 for both PFS (HR 0.79 [0.56, 1.10] and OS (HR: 0.72 [0.50, 1.05]). NIVO+RELA showed significantly improved PFS versus NIVO (HR 0.81 [0.67, 0.97]), but the upper bound of the CrI crossed 1 for OS (HR 0.82 [0.67, 1.01]). Safety analyses showed NIVO+RELA had improved safety outcomes compared to NIVO1+IPI3 for both all-cause (OR 0.46 [0.29, 0.72]) and treatment-related grade 3/4 AEs (OR 0.43 [0.25, 0.73], but had a higher odds of treatment-related grade 3/4 versus PEM (OR 1.99 [1.01, 3.87]) and NIVO (OR 2.08 [1.39, 3.14]). Results were directionally consistent in the PD-L1<1% population, and when time-varying analyses were considered.

CONCLUSIONS: NIVO+RELA provides an important treatment option for 1L advanced or unresectable/metastatic melanoma; in particular, NIVO+RELA has similar efficacy with a lower rate of grade 3/4 AEs compared with NIVO1+IPI3.