3 Key Takeaways
Plain English Summary- 01Core Finding
Here we report data from RELATIVITY-047 with the longest follow-up at present.
- 02Study Evidence
Tested in a randomized controlled trial (n = 355) at the Phase III stage.
- 03Practical Meaning
The addition of relatlimab to nivolumab was associated with a lower prevalence of primary resistance than nivolumab alone.
What This Means for You
The safety profile remained consistent with prior reports. Among biomarker (measurable biological signal)-evaluable patients in the PD-L1 ≥a clinically meaningful level subgroup, analyses revealed an association between worse outcomes with nivolumab and high peripheral or tumor LAG-3 + CD8 cell levels. The addition of relatlimab to nivolumab was associated with a lower prevalence of primary resistance than nivolumab alone. These data support the hypothesis that relatlimab can overcome LAG-3-mediated resistance to nivolumab and provide evidence for differential efficacy (real-world effectiveness in the trial) patterns observed across biomarker subgroups linked to primary versus acquired resistance states. ClinicalTrials.gov identifier: NCT03470922.
The Discovery
Nivolumab plus relatlimab is approved for advanced melanoma based on the RELATIVITY-047 trial; however, long-term data are needed. Here we report data from RELATIVITY-047 with the longest follow-up at present. In this Phase 2-3, double-blind trial, patients with metastatic/unresectable melanoma were randomized 1:1 to nivolumab 480 mg plus relatlimab 160 mg (n = 355) or nivolumab 480 mg (n = 359) intravenously every 4 weeks. The primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints were overall survival (OS), response and safety. Additional post hoc analyses, such as melanoma-specific survival (MSS) and exploratory biomarker (measurable biological signal) analyses, are also reported. This analysis shows clear separation in survival curves with the largest absolute differences to date in PFS, OS and MSS. In this prespecified 5-year analysis, with a minimum follow-up of 57.3 months, nivolumab plus relatlimab demonstrated continued clinically significant benefit versus nivolumab for PFS (hazard ratio (HR) = 0.77; 95% confidence interval (CI): 0.65-0.92), OS (HR = 0.78; 95% CI: 0.64-0.95) and MSS (HR = 0.71; 95% CI: 0.57-0.88). The safety profile remained consistent with prior reports.
How It Works, Simply
This infectious disease research focuses on blood biomarker (measurable biological signal). Researchers evaluated it using a randomized controlled trial (n = 355) at the Phase III stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Here we report data from RELATIVITY-047 with the longest follow-up at present.
- 02Study Evidence
Tested in a randomized controlled trial (n = 355) at the Phase III stage.
- 03Practical Meaning
The addition of relatlimab to nivolumab was associated with a lower prevalence of primary resistance than nivolumab alone.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (n = 355) · Phase III
Biological Pathway & Modality
Blood biomarker
Intervention: Relatlimab plus nivolumab versus nivolumab for advanced melanoma: 5-year survival
Experimental Findings & Endpoints
Nivolumab plus relatlimab is approved for advanced melanoma based on the RELATIVITY-047 trial; however, long-term data are needed.
Here we report data from RELATIVITY-047 with the longest follow-up at present. In this Phase 2-3, double-blind trial, patients with metastatic/unresectable melanoma were randomized 1:1 to nivolumab 480 mg plus relatlimab 160 mg (n = 355) or nivolumab 480 mg (n = 359) intravenously every 4 weeks.
The primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints were overall survival (OS), response and safety.
Additional post hoc analyses, such as melanoma-specific survival (MSS) and exploratory biomarker analyses, are also reported. This analysis shows clear separation in survival curves with the largest absolute differences to date in PFS, OS and MSS.
In this prespecified 5-year analysis, with a minimum follow-up of 57.3 months, nivolumab plus relatlimab demonstrated continued clinically significant benefit versus nivolumab for PFS (hazard ratio (HR) = 0.77; 95% confidence interval (CI): 0.65-0.92), OS (HR = 0.78; 95% CI: 0.64-0.95) and MSS (HR = 0.71; 95% CI: 0.57-0.88). The safety profile remained consistent with prior reports.
Clinical Translation & Practice Context
The safety profile remained consistent with prior reports.
Among biomarker-evaluable patients in the PD-L1 ≥a clinically meaningful level subgroup, analyses revealed an association between worse outcomes with nivolumab and high peripheral or tumor LAG-3 + CD8 cell levels. The addition of relatlimab to nivolumab was associated with a lower prevalence of primary resistance than nivolumab alone.
These data support the hypothesis that relatlimab can overcome LAG-3-mediated resistance to nivolumab and provide evidence for differential efficacy patterns observed across biomarker subgroups linked to primary versus acquired resistance states. ClinicalTrials.gov identifier: NCT03470922.
The Bottom Line · Clinical Pearl
“ClinicalTrials.gov identifier: NCT03470922 .”
Published in Nature Medicine · Current Stage: Phase III