Site Editor
Soo Park, MD
Soo Park, MD
Posted: Monday, March 3, 2025
Dual checkpoint inhibition immunotherapy for advanced melanoma treatment continued to outperform monotherapy, according to 3-year follow-up data from the global phase II/III RELATIVITY-047 trial. The study, conducted by Hussein A. Tawbi, MD, PhD, of The University of Texas MD Anderson Cancer Center, and published in the Journal of Clinical Oncology, compared nivolumab plus relatlimab, a fixed-dose combination targeting both PD-1 and LAG-3, with nivolumab monotherapy in patients with unresectable or metastatic melanoma.
“Although targeting two immune checkpoints in patients with advanced melanoma is a well-established treatment strategy, to our knowledge, RELATIVITY-047 is the first study to test and show a statistically significant improvement in progression-free survival for an immunotherapy combination vs PD-1 monotherapy,” the investigators wrote.
The RELATIVITY-047 trial included 714 patients randomly assigned 1:1 with stratification based on LAG-3 expression, PD-L1 expression, BRAF mutation status, and metastasis stage to receive either nivolumab (480 mg) plus relatlimab (160 mg) or nivolumab (480 mg) alone, administered intravenously every 4 weeks. The study’s primary endpoint was progression-free survival, with secondary endpoints including overall survival and objective response rate.
With a median follow-up of 33.8 months, the study demonstrated sustained benefits from the combination therapy, with a median progression-free survival of 10.2 months for patients receiving nivolumab plus relatlimab compared with 4.6 months for patients receiving nivolumab alone. The 3-year progression-free survival rates were 31.8% and 26.9%, respectively. In addition, the study authors noted, “a sustained benefit was observed with nivolumab plus relatlimab in patients with high lactate dehydrogenase, high tumor burden, stage M1C disease, and mucosal and acral melanoma subtypes, where combination immunotherapy may be considered.”
The safety findings remained consistent with prior reports, with no new signals emerging over the extended follow-up period. Grade 3 or 4 treatment-related adverse events were noted for 22% of patients in the combination arm compared with 12% for the patients receiving nivolumab alone.
Disclosure: For full disclosures of the other study authors visit ascopubs.org.
JNCCN Spotlights
