{"entity":{"id":"fianlimab-phase3-melanoma","kind":"trial","name":"Fianlimab + cemiplimab phase 3 (first-line melanoma)","aka":[],"tldr":"A second LAG-3 blocker failed to beat pembrolizumab alone, a warning that the Opdualag result is not automatically a class effect.","summary":"Regeneron reported that the trial missed its primary PFS endpoint; the high-dose combination improved median PFS numerically by 5.1 months, but the difference was not statistically significant. Differences from RELATIVITY-047 include the comparator (pembrolizumab rather than nivolumab), the antibody, and dosing. The adjuvant fianlimab phase 3 continues.","status":"negative","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05352672","url":"https://clinicaltrials.gov/study/NCT05352672"},{"label":"Regeneron update","url":"https://investor.regeneron.com/news-releases/news-release-details/regeneron-provides-update-phase-3-trial-fianlimab-lag-3"}],"tags":["failure","lesson:class-effect-not-guaranteed"],"related":[],"cancers":["melanoma","advanced-melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["lag3","pd1"],"drugs":["fianlimab","cemiplimab","pembrolizumab"],"companies":["regeneron"],"institutions":[],"pathways":[],"terms":[],"trials":["relativity-047"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05352672","phase":"3","setting":"Untreated unresectable or metastatic melanoma: fianlimab + cemiplimab (two dose levels) vs pembrolizumab","sponsor":"Regeneron","result":"Primary PFS endpoint not met; numerical +5.1 months median PFS at the high dose.","started":"2022-07-14","startedType":"actual","yearReported":2026,"enrolled":1546,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival, fianlimab 1600 mg + cemiplimab vs pembrolizumab","primary":true,"unit":"months","arms":[{"name":"Fianlimab 1600 mg + cemiplimab","n":508,"value":11.5,"note":"Not significant; primary endpoint not met"},{"name":"Pembrolizumab","n":462,"value":6.4}],"hr":0.845,"ci":[0.709,1.008],"p":"0.0627","source":"https://www.cancernetwork.com/view/fianlimab-combo-does-not-significantly-improve-pfs-in-advanced-melanoma"},{"endpoint":"Progression-free survival, fianlimab 400 mg + cemiplimab vs pembrolizumab","primary":true,"unit":"months","arms":[{"name":"Fianlimab 400 mg + cemiplimab","n":422,"value":9.6,"note":"Not significant"},{"name":"Pembrolizumab","n":462,"value":6.4}],"hr":0.931,"ci":[0.773,1.112],"p":"0.4661","source":"https://www.cancernetwork.com/view/fianlimab-combo-does-not-significantly-improve-pfs-in-advanced-melanoma"},{"endpoint":"Progression-free survival, cemiplimab monotherapy arm","unit":"months","arms":[{"name":"Cemiplimab","n":154,"value":6.3}],"source":"https://www.cancernetwork.com/view/fianlimab-combo-does-not-significantly-improve-pfs-in-advanced-melanoma"}],"replication":"Second LAG-3 setback after RELATIVITY-098; the numerical PFS gain at the high dose did not reproduce the phase 1 signal, and RELATIVITY-047 remains the only positive randomised LAG-3 trial in melanoma."},"route":"/trials/fianlimab-phase3-melanoma/","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":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"},{"id":"fianlimab","kind":"drug","name":"Fianlimab","route":"/drugs/fianlimab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"regeneron","kind":"company","name":"Regeneron","route":"/companies/regeneron/"}],"trial":[{"id":"relativity-047","kind":"trial","name":"RELATIVITY-047","route":"/trials/relativity-047/"}],"pairing":[{"id":"lag3-adjuvant-caution","kind":"pairing","name":"Caution: LAG-3 blockade outside active disease","route":"/pairings/lag3-adjuvant-caution/"}],"idea":[{"id":"idea-tr1-extended-interval-checkpoint-dosing","kind":"idea","name":"Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable","route":"/ideas/idea-tr1-extended-interval-checkpoint-dosing/"},{"id":"idea-chronotherapy-immunotherapy","kind":"idea","name":"Give immunotherapy in the morning","route":"/ideas/idea-chronotherapy-immunotherapy/"},{"id":"idea-microbiome-io-fmt","kind":"idea","name":"Microbiome transplant as a routine immunotherapy adjunct","route":"/ideas/idea-microbiome-io-fmt/"},{"id":"idea-tr1-immunotherapy-stop-trials","kind":"idea","name":"Randomised trials of stopping immunotherapy after one year versus continuing","route":"/ideas/idea-tr1-immunotherapy-stop-trials/"}]}}