Three-Year Overall Survival With Nivolumab Plus Relatlimab in Advanced Melanoma From RELATIVITY-047

Abstract

Nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), along with a clinically meaningful, but not statistically significant improvement in overall survival (OS) and a numerically higher objective response rate (ORR) compared with nivolumab in the RELATIVITY-047 trial (ClinicalTrials.gov identifier: NCT03470922). We report updated descriptive efficacy and safety results from RELATIVITY-047 with a median follow-up of 33.8 months. Median PFS was 10.2 months (95% CI, 6.5 to 15.4) with nivolumab plus relatlimab and 4.6 months (95% CI, 3.5 to 6.5) with nivolumab (hazard ratio [HR], 0.79 [95% CI, 0.66 to 0.95]); median OS was 51.0 months (95% CI, 34.0 to not reached) and 34.1 (95% CI, 25.2 to 44.7) months, respectively (HR, 0.80 [95% CI, 0.66 to 0.99]). ORR was 43.7% (95% CI, 38.4 to 49.0) with nivolumab plus relatlimab and 33.7% (95% CI, 28.8 to 38.9) with nivolumab. Efficacy across the majority of prespecified subgroups favored the combination. No new or unexpected safety signals were identified. Overall, at 3-year follow-up, the benefit observed with nivolumab plus relatlimab compared with nivolumab in patients with advanced melanoma was sustained, with the OS HR 95% CI upper bound now <1. This benefit is accompanied by a safety profile consistent with previous reports.

FIG 1.

CONSORT diagram.

FIG 2.

Kaplan–Meier estimates of (A) PFS and (B) OS. BICR, blinded independent central review; HR, hazard ratio; NR, not reached; OS, overall survival; PFS, progression-free survival.

FIG 3.

(A) Response to treatment and Kaplan–Meier estimates of (B) MSS^a and (C) PFS2. ^aA total of 375 deaths (52.5%) were reported (173 [48.7%] in the nivolumab plus relatlimab arm and 202 [56.3%] in the nivolumab arm), with 133/355 (37.5%) and 166/359 (46.2%) deaths due to melanoma reported in the nivolumab plus relatlimab arm and nivolumab arm (nonmelanoma deaths occurred in 40 patients [11.3%] and 36 patients [10.0%]), respectively. MSS was defined as the time from random assignment to death due to melanoma per investigator assessment, with deaths for any other reason, including death due to study drug toxicity, being censored. PFS2 was defined as the time from random assignment to progression after the next line of therapy, per investigator assessment, or to death from any cause, whichever occurred first. CR, complete response; HR, hazard ratio; MSS, melanoma-specific survival; NR, not reached; PD, progressive disease; PFS2, progression-free survival-2; PR, partial response; SD, stable disease.