Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update
Evan J. Lipson, F. Stephen Hodi, Hussein Tawbi, Dirk Schadendorf, Paolo A. Ascierto, Luis Matamala, Erika Castillo Gutiérrez, Piotr Rutkowski, Helen Gogas, Cristopher Lao, J. Menezes, Stéphane Dalle, Ana Arance, Caroline Gaudy‐Marqueste, Bohang Chen, William T. Jackson, Sourav Mukherjee, Sonia Dolfi, Georgina V. Long
Abstract
BACKGROUND: In phase 2/3 randomized RELATIVITY-047, nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), a clinically meaningful but not statistically significant improvement in overall survival (OS), and a numerically higher objective response rate (ORR) versus nivolumab alone in patients with previously untreated advanced melanoma. METHODS: Descriptive 4-year updated analyses in patients treated with nivolumab 480 mg plus relatlimab 160 mg fixed-dose combination versus nivolumab 480 mg intravenously every 4 weeks are presented. Primary endpoint was PFS by blinded independent central review (BICR). Other endpoints included melanoma-specific survival (MSS). RESULTS: At 45.3 months' minimum follow-up, nivolumab plus relatlimab versus nivolumab PFS improvement was maintained: 4-year PFS rates were 30.6 % (95 % CI, 25.4-35.9) versus 23.6 % (95 % CI, 18.9-28.5); OS was numerically better with 4-year OS rates of 52.0 % (95 % CI, 46.6-57.1) versus 42.8 % (95 % CI, 37.5-47.9); and ORR difference was maintained at 43.9 % (95 % CI, 38.7-49.3) versus 33.4 % (95 % CI, 28.6-38.6), respectively. 4-year MSS rates were 59.7 % (95 % CI, 54.1-64.8) for nivolumab plus relatlimab and 49.6 % (95 % CI, 44.0-54.9) for nivolumab. Efficacy across the majority of prespecified subgroups favored the combination. No new or unexpected safety signals were identified. CONCLUSIONS: With 4 years of follow-up, nivolumab plus relatlimab demonstrated durable improvement in outcomes versus nivolumab monotherapy for patients with previously untreated advanced melanoma. The durable benefit observed comes at a lower toxicity cost compared with other immuno-oncology combinations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03470922.