Nivolumab (NIVO) plus relatlimab (RELA) vs. NIVO in previously untreated, metastatic, or unresectable melanoma (RELATIVITY-047): 3- year overall survival (OS) and melanoma-specific survival (MSS) results.

Tawbi HA, Hodi S, Lipson EJ, Schadendorf D, Ascierto PA, Matamala L, Castillo Gutiérrez E, Rutkowski P, Gogas HJ, Lao CD, De Menezes JJ, Dalle S, Arance AM, Grob JJ, Ratto B, Rodriguez S, Mazzei A, Dolfi S, Long G. Annals of Dermatology and Venereology – FMC, 4, no. 8, Supplement 1, (Dec 01 2024): A349-A50, doi:https://doi.org/10.1016/j.fander.2024.09.415.

Abstract

Introduction:

The fixed-dose combination (FDC) of NIVO  +  RELA demonstrated a statistically significant progression-free survival (PFS) benefit compared to NIVO monotherapy in the RELATIVITY-047 study ( NCT03470922 ), a non-statistically significant increase in OS, and a numerically higher objective response rate (ORR), leading to regulatory approval of the FDC of NIVO  +  RELA. Here, we present updated descriptive analyses after 3  years of follow-up.

Materials and Methods: 

Patients (pts) were randomized 1:1 to receive NIVO 480  mg  +  RELA 160  mg FDC or NIVO 480  mg monotherapy every 4 weeks. PFS per RECIST v1.1 was assessed by blinded independent central review (BICR); secondary endpoints included OS and ORR per BICR. Exploratory analyses included MSS (melanoma-related death, with censoring of deaths due to other causes), CNS metastasis-free survival in specified populations, and efficacy on subsequent systemic therapy.

Results: 

At data cutoff (October 19, 2023), the median follow-up was 33.8 months (range, 0.3 to 64.2 months). NIVO  +  RELA continued to demonstrate superiority over NIVO in terms of PFS, OS, ORR, and MSS. In the majority of key subgroups, results also favored NIVO  +  RELA over NIVO. Subsequent systemic therapy was received by 135 patients (38%) in NIVO  +  RELA and 141 patients (39%) in NIVO. Grade 3-4 treatment-emergent adverse events (TRAEs) occurred in 78 patients (22%) in NIVO  +  RELA and 43 patients (12%) in NIVO; TRAEs (any grade) led to treatment discontinuation in 63 patients (18%) and 35 patients (10%), respectively. No new treatment-related deaths have been reported since the last analysis.

Discussion:

After 3  years of follow-up, NIVO  +  RELA continued to show superiority over NIVO in terms of PFS, OS, ORR, and MSS. OS and MSS demonstrated sustained improvement, with an upper limit of the Hazard Ratio (95% CI) for OS  <  1. Efficacy results also continued to favor NIVO  +  RELA over NIVO in the majority of prespecified subgroups. The safety of NIVO  +  RELA remained consistent with previous results, with no new or unexpected safety signals. CNS metastasis-free survival and efficacy results with subsequent systemic therapy will be presented.

Conclusions: 

After 3  years of follow-up, NIVO  +  RELA continued to show superiority over NIVO in terms of PFS, OS, ORR and MSS.