An extended analysis of the phase II/III RELATIVITY-047 trial demonstrates a significant overall survival (OS) benefit with the combination of nivolumab and relatlimab compared to nivolumab alone in patients with previously untreated, unresectable advanced stage III or IV melanoma. The findings, published in the Journal of Clinical Oncology, highlight the sustained efficacy and manageable safety profile of this dual immunotherapy approach.
The global trial randomized 714 patients to receive either a fixed-dose combination of nivolumab (480 mg) and relatlimab (160 mg) or nivolumab (480 mg) every 4 weeks. After a median follow-up of 33.8 months, the combination therapy showed a marked improvement in median overall survival, reaching 51.0 months (95% CI, 34.0 months to not reached) compared to 34.1 months (95% CI, 25.2 to 44.7 months) with nivolumab alone (HR = 0.80, 95% CI = 0.66–0.99).
Sustained Survival Advantage
The 3-year overall survival rates further underscored the benefit, with 54.6% (95% CI, 49.2%–59.6%) in the nivolumab/relatlimab arm versus 48.0% (95% CI, 42.7%–53.1%) in the nivolumab arm. Melanoma-specific survival also favored the combination, with a median not reached (95% CI = not reached to not reached) compared to 46.7 months (95% CI = 34.1 months to not reached) in the nivolumab group (HR = 0.75, 95% CI = 0.60–0.94).
Progression-Free Survival and Response Rates
The study also reported a significant improvement in median progression-free survival (PFS) with the combination therapy, demonstrating 10.2 months (95% CI = 6.5–15.4 months) compared to 4.6 months (95% CI = 3.5–6.5 months) in the nivolumab group (HR = 0.79, 95% CI = 0.66–0.95). The 3-year PFS rate was 31.8% versus 26.9%, respectively. Additionally, the objective response rate (ORR) was higher in the nivolumab/relatlimab group at 43.7% compared to 33.7% in the nivolumab group.
Safety Profile
The extended analysis revealed no new or unexpected safety signals, confirming the tolerability of the nivolumab/relatlimab combination. The safety profile was consistent with previous reports, indicating that the combination can be safely administered in the first-line setting for advanced melanoma.
Clinical Implications
Hussein A. Tawbi, MD, PhD, of The University of Texas MD Anderson Cancer Center, the corresponding author of the study, noted, "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 overall survival hazard ratio 95% CI upper bound now < 1. This benefit is accompanied by a safety profile consistent with previous reports."
The RELATIVITY-047 trial's findings support the use of nivolumab/relatlimab as a preferred first-line treatment option for patients with advanced melanoma, offering a significant and sustained improvement in overall survival compared to nivolumab monotherapy. This combination provides clinicians with an effective and well-tolerated immunotherapy regimen for this patient population.
