{"entity":{"id":"cosmic-313","kind":"trial","name":"COSMIC-313","aka":[],"tldr":"The first triplet trial in kidney cancer slowed progression but did not help patients live longer, and added toxicity.","summary":"COSMIC-313, trial NCT03937219 sponsored by Exelixis and reported in 2022, was the first triplet trial in kidney cancer, and it slowed progression but did not help patients live longer while adding toxicity. It randomised 855 patients with untreated intermediate or poor-risk clear-cell renal cell carcinoma to cabozantinib plus nivolumab and ipilimumab or the doublet alone, met its primary progression-free survival endpoint, but showed no overall survival difference at the final analysis with far more severe adverse events, and poor-risk patients did not benefit even on progression; the triplet was not approved. OnCo links it to renal cell carcinoma, cabozantinib, nivolumab, ipilimumab and Sumanta K. Pal. Whether any third agent can add to an immunotherapy doublet is the open question.","status":"mixed","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03937219","url":"https://clinicaltrials.gov/study/NCT03937219"}],"tags":["lesson:pfs-without-os"],"related":[],"cancers":["rcc"],"sections":[],"technologies":["antiangiogenic","kinase-inhibitors"],"targets":[],"drugs":["cabozantinib","nivolumab","ipilimumab"],"companies":["exelixis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["sumanta-pal"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03937219","phase":"3","setting":"Untreated intermediate/poor-risk clear-cell RCC: cabozantinib + nivolumab + ipilimumab vs nivolumab + ipilimumab","sponsor":"Exelixis","result":"PFS HR 0.73; OS HR 1.02 (no benefit).","started":"2019-06-25","startedType":"actual","yearReported":2022,"enrolled":855,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"arms":[{"name":"Cabozantinib + nivolumab + ipilimumab","n":428},{"name":"Nivolumab + ipilimumab","n":427}],"hr":0.73,"ci":[0.57,0.94],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2212851"},{"endpoint":"Overall survival (final)","unit":"months","arms":[{"name":"Triplet","value":41.9},{"name":"Doublet","value":42}],"hr":1.02,"ci":[0.85,1.23],"source":"https://www.annalsofoncology.org/article/S0923-7534(26)00067-0/fulltext"}],"replication":"Consistent with LITESPARK-012: first-line triplets have not improved OS in RCC."},"route":"/trials/cosmic-313/","neighbours":{"cancer":[{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","route":"/drugs/cabozantinib/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"company":[{"id":"exelixis","kind":"company","name":"Exelixis","route":"/companies/exelixis/"}],"person":[{"id":"sumanta-pal","kind":"person","name":"Sumanta K. Pal","route":"/people/sumanta-pal/"}]}}