RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma
Adding an antibody against a second immune brake, LAG-3, to nivolumab delayed progression in advanced melanoma compared with nivolumab alone, with far fewer serious side effects than the ipilimumab combination.
Double-blind phase 3 trial of 714 patients with untreated advanced melanoma randomised to a fixed-dose combination of relatlimab (anti-LAG-3) and nivolumab or nivolumab alone. Primary endpoint was PFS by blinded review.
Median PFS was 10.1 vs 4.6 months (HR 0.75). Grade 3-4 treatment-related adverse events were 18.9% vs 9.7%, much lower than the roughly 55-59% seen with nivolumab plus ipilimumab. It validated LAG-3 as the third checkpoint target after CTLA-4 and PD-1, led to FDA approval of the combination (Opdualag) in 2022, and provided a gentler dual-checkpoint option.
- Median PFS 10.1 vs 4.6 months; HR 0.75 (95% CI 0.62-0.92); 12-month PFS 47.7% vs 36.0%.
- Benefit consistent across LAG-3 and PD-L1 expression subgroups, so neither is used for selection.
- Grade 3-4 treatment-related adverse events 18.9% vs 9.7%; discontinuation for toxicity 14.6% vs 6.7%.
- Overall survival (updated analysis): median 51.0 vs 34.1 months, HR 0.80, not meeting the prespecified significance threshold.
- Objective response 43.1% vs 32.6% in later analyses.
Patients with newly diagnosed advanced melanoma have a dual-checkpoint option that improves on nivolumab alone with only a modest increase in serious side effects, making it attractive for those unable to tolerate or unwilling to risk the toxicity of ipilimumab. It did not prove superior survival, and it has not been compared with nivolumab plus ipilimumab, which remains preferred for patients with brain metastases or other high-risk features. LAG-3 is now an established target under study in many other cancers.
- Overall survival improvement did not reach statistical significance.
- No head-to-head comparison with nivolumab plus ipilimumab; indirect comparisons suggest the ipilimumab combination may be more active in poor-prognosis subgroups.
- Patients with active brain metastases were excluded.
- Whether relatlimab adds benefit in other tumours is not yet demonstrated in phase 3.
Pages like this
not linked directly; found by shared links- Key paperCheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade later
Shares CheckMate 067, Relatlimab + nivolumab, LAG-3, Immune-related adverse events (irAEs).
- Key paperCheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma
Shares CheckMate 067, Relatlimab + nivolumab, Immune-related adverse events (irAEs), Bristol Myers Squibb.
- InstitutionIstituto Nazionale Tumori IRCCS Fondazione G. Pascale
Shares CheckMate 067, Relatlimab + nivolumab, LAG-3, Bristol Myers Squibb.
- TrialRELATIVITY-047
Shares CheckMate 067, Relatlimab + nivolumab, LAG-3, Nivolumab.
- Key paperKEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation
Shares Lines of therapy, Immune-related adverse events (irAEs), Overall survival (OS), Progression-free survival (PFS).
- TrialRELATIVITY-098
Shares Relatlimab + nivolumab, LAG-3, Nivolumab, Melanoma.
- Key paperCheckMate 649: nivolumab plus chemotherapy as first treatment for advanced gastric, gastro-oesophageal junction and oesophageal adenocarcinoma
Shares Lines of therapy, Bristol Myers Squibb, Overall survival (OS), Progression-free survival (PFS).
- Key paperCLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer
Shares Lines of therapy, Too many combinations to test, Overall survival (OS), Progression-free survival (PFS).