Background: NIVO + RELA and NIVO + IPI are approved as dual checkpoint inhibitor, 1L treatment options for patients (pts) with advanced melanoma based on results from the RELATIVITY-047 (NIVO + RELA vs NIVO; enrollment, 2018–2020) and CheckMate 067 (NIVO + IPI or NIVO vs IPI; enrollment, 2013–2014) trials, respectively. However, there is no head-to-head trial comparing the combinations; therefore, this ITC was conducted using PLD. Methods: To adjust for cross-trial imbalances in baseline characteristics, inverse probability of treatment weighting (IPTW) was used. Database locks were selected to best align follow-ups in RELATIVITY-047 (min., 21 mo; median, 25 mo) and CheckMate 067 (min., 28 mo; median, 29 mo). Efficacy and safety outcomes were selected based on data availability, including progression-free survival (PFS) per investigator, confirmed objective response rates (ORRs) per investigator, overall survival (OS), treatment-related adverse events (TRAEs), and TRAEs leading to discontinuation (DC). Efficacy was also evaluated in key subgroups. PFS and OS were compared for NIVO + RELA vs NIVO + IPI using Kaplan–Meier curves and hazard ratios (HRs); ORRs were compared using odds ratio (OR). As an internal validation of the ITC and matched assessments, the weighted NIVO cohorts from both trials were compared. Results: After IPTW, key baseline characteristics were balanced for NIVO + RELA (n = 340) and NIVO + IPI (n = 298). PFS, confirmed ORR, and OS after IPTW were similar between the treatments (table). Efficacy outcomes appeared to be similar between the treatments across subgroups, although trends favoring NIVO + IPI were observed for certain subgroups, such as pts with BRAF mutant disease or lactate dehydrogenase more than twice the upper limit of normal. Grade 3/4 TRAEs occurred in 23% and 61% of pts receiving NIVO + RELA and NIVO + IPI, respectively; any-grade TRAEs leading to DC occurred in 17% and 40% of pts. Efficacy outcomes were similar between the NIVO cohorts (table). Conclusions: In the absence of head-to-head trials, this ITC suggests that 1L treatment with NIVO + RELA may have comparable efficacy to, and better tolerability than, NIVO + IPI in pts with advanced melanoma. Similar outcomes between the NIVO cohorts support the ITC methodology. Results should be interpreted with caution given differences in study design and changes in treatment landscape over time.

NR, not reached.