Dr Tawbi on Nivolumab Plus Relatlimab in Metastatic Melanoma

Hussein A. Tawbi, MD, PhD, professor, deputy chair, director, Personalized Cancer Therapy, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the 2-year findings from the phase 2/3 RELATIVITY-047 trial (NCT03470922) of nivolumab plus relatlimab-rmbw (Opdualag) in treatment-naïve patients with metastatic or unresectable melanoma.

RELATIVITY-047 investigated the combination of the PD-1 inhibitor nivolumab and the LAG-3 inhibitor relatlimab vs nivolumab alone in previously untreated patients with unresectable or metastatic melanoma. The primary end point of this trial was progression-free survival (PFS), with key secondary end points including overall survival (OS) and overall response rate.

At a median follow-up of 25.3 months, the median PFS was 10.2 months with the combination (n = 355) compared with 4.6 months with nivolumab alone (n = 359), equating to a hazard ratio (HR) of 0.81. In addition, the 1-year PFS rates were 48% with the combination vs 37% with nivolumab monotherapy, and the 3-year PFS rates were 31% and 27%, respectively.

Furthermore, updated OS data demonstrated a consistent decrease in the risk of death with the combination, although these findings are from exploratory analyses and thus not statistically significant, Tawbi notes. The median OS was not reached in the nivolumab/relatlimab arm vs 33.2 months in the nivolumab monotherapy arm, translating to a HR of 0.82.

This trial also evaluated outcomes in patients who have progressed on subsequent therapy (PFS2). This PFS2 analysis was important for determining the effects of nivolumab plus relatlimab on second-line combinations such as CTLA-4 inhibitors and PD-1 inhibitors, Tawbi explains. Both arms of the trial experienced similar PFS2 outcomes, at a median of 28.4 months and 20.1 months in the nivolumab/relatlimab and nivolumab monotherapy arms, respectively. The median PFS2 in the combination arm was consistent with PFS outcomes expected with CTLA-4/PD-1 combinations in the frontline setting, according to Tawbi.

In the subset of patients with BRAF-mutant disease who were treated with BRAF and MEK inhibitors in the second line following treatment with nivolumab plus relatlimab, the median PFS was 15.4 months in the nivolumab/relatlimab arm (n = 43) and 10.6 months in the nivolumab monotherapy arm (n = 45), showing that frontline nivolumab plus relatlimab did not negatively affect the efficacy of subsequent BRAF- and MEK-directed therapy, Tawbi concludes.

Disclosures: Dr Tawbi reports consulting or advisory roles with Boxer Capital, Bristol-Myers Squibb, Eisai, Genentech/Roche, Iovance Biotherapeutics, Jazz Pharmaceuticals, Karyopharm Therapeutics, Medicenna, Merck, Novartis, and Pfizer; and research funding from Bristol-Myers Squibb (Inst), Celgene (Inst), Dragonfly Therapeutics (Inst), Genentech/Roche (Inst), GlaxoSmithKline (Inst), Merck (Inst), Novartis (Inst), and RAPT Therapeutics (Inst).