{"entity":{"id":"relativity-047","kind":"trial","name":"RELATIVITY-047","aka":[],"tldr":"Proved that adding a LAG-3 blocker to PD-1 blockade delays progression, with far less toxicity than the ipilimumab combination.","summary":"PFS 10.1 vs 4.6 months (HR 0.75) led to FDA approval of Opdualag in March 2022. OS was not formally significant at first analysis; extended follow-up reported median OS 51.0 vs 34.1 months with 3-year OS 54.6% vs 48.0% (JCO 2024) and a 4-year update (EJC 2025) with the upper confidence bound below 1. Grade 3-4 treatment-related events ~21% versus ~59% for nivolumab-ipilimumab in CheckMate 067.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03470922","url":"https://clinicaltrials.gov/study/NCT03470922"},{"label":"3-year OS, JCO 2024","url":"https://ascopubs.org/doi/10.1200/JCO.24.01124"},{"label":"4-year update, EJC 2025","url":"https://www.ejcancer.com/article/S0959-8049(25)00329-6/fulltext"}],"tags":[],"related":[],"cancers":["melanoma","advanced-melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["lag3","pd1"],"drugs":["relatlimab-nivolumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-067"],"people":["hussein-tawbi"],"bottlenecks":[],"keyPapers":["paper-relativity-047-nejm-2022","paper-relativity-047-nejm-evid-2023-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03470922","phase":"2/3","setting":"Untreated unresectable or metastatic melanoma: nivolumab + relatlimab (fixed dose) vs nivolumab","sponsor":"BMS","result":"PFS HR 0.75; median OS 51.0 vs 34.1 months.","started":"2018-04-11","startedType":"actual","yearReported":2022,"enrolled":714,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Nivolumab + relatlimab","value":10.1},{"name":"Nivolumab","value":4.6}],"hr":0.75,"source":"https://ascopubs.org/doi/10.1200/JCO.24.01124"},{"endpoint":"Overall survival (3-year)","unit":"%","arms":[{"name":"Nivolumab + relatlimab","value":54.6},{"name":"Nivolumab","value":48}],"source":"https://ascopubs.org/doi/10.1200/JCO.24.01124"}],"replication":"No independent phase 3 yet; the adjuvant RELATIVITY-098 trial of the same combination was negative, so the benefit appears specific to the advanced setting."},"route":"/trials/relativity-047/","neighbours":{"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"lag3","kind":"target","name":"LAG-3","route":"/targets/lag3/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/"}],"trial":[{"id":"checkmate-067","kind":"trial","name":"CheckMate 067","route":"/trials/checkmate-067/"},{"id":"fianlimab-phase3-melanoma","kind":"trial","name":"Fianlimab + cemiplimab phase 3 (first-line melanoma)","route":"/trials/fianlimab-phase3-melanoma/"}],"person":[{"id":"hussein-tawbi","kind":"person","name":"Hussein A. Tawbi","route":"/people/hussein-tawbi/"}],"paper":[{"id":"paper-checkmate-067-10-year-nejm-2025","kind":"paper","name":"CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma","route":"/key-papers/paper-checkmate-067-10-year-nejm-2025/"},{"id":"paper-relativity-047-nejm-evid-2023-update","kind":"paper","name":"Overall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma","route":"/key-papers/paper-relativity-047-nejm-evid-2023-update/"},{"id":"paper-relativity-047-nejm-2022","kind":"paper","name":"RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma","route":"/key-papers/paper-relativity-047-nejm-2022/"}],"pairing":[{"id":"lag3-adjuvant-caution","kind":"pairing","name":"Caution: LAG-3 blockade outside active disease","route":"/pairings/lag3-adjuvant-caution/"}]}}