{"entity":{"id":"contact-03","kind":"trial","name":"CONTACT-03","aka":[],"tldr":"Continuing immunotherapy after it has failed, alongside a targeted pill, added nothing but side effects. The first definitive test of 'IO rechallenge'.","summary":"CONTACT-03, trial NCT04338269 sponsored by Roche and Exelixis and published in the Lancet in 2023, was the first definitive test of immunotherapy rechallenge in kidney cancer, and it found that continuing PD-L1 blockade after progression on immunotherapy, alongside cabozantinib, added nothing but side effects. It randomised 522 patients with advanced renal cell carcinoma progressing on or after a PD-1 or PD-L1 inhibitor to atezolizumab plus cabozantinib or cabozantinib alone and found no difference in progression-free or overall survival with more toxicity. OnCo links it to renal cell carcinoma, atezolizumab, cabozantinib, Sumanta K. Pal, Neeraj Agarwal and a caution pairing about PD-1 rechallenge after progression. It changed practice so that rechallenge is no longer recommended, and whether any biomarker-defined subgroup might still benefit is the open question.","status":"negative","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04338269","url":"https://clinicaltrials.gov/study/NCT04338269"}],"tags":["lesson:io-rechallenge"],"related":[],"cancers":["rcc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["atezolizumab","cabozantinib"],"companies":["exelixis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["sumanta-pal","neeraj-agarwal"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04338269","phase":"3","setting":"Advanced RCC progressing on or after a PD-1/PD-L1 inhibitor: atezolizumab + cabozantinib vs cabozantinib","sponsor":"Roche / Exelixis","result":"PFS HR 1.03; OS HR 0.94, negative.","started":"2020-07-28","startedType":"actual","yearReported":2023,"enrolled":522,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Atezolizumab + cabozantinib","n":263,"value":10.6},{"name":"Cabozantinib","n":259,"value":10.8}],"hr":1.03,"ci":[0.83,1.28],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00922-4/fulltext"}],"replication":"Replicated by TiNivo-2 (2024-26): no benefit from nivolumab rechallenge with tivozanib."},"route":"/trials/contact-03/","neighbours":{"cancer":[{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","route":"/drugs/cabozantinib/"}],"company":[{"id":"exelixis","kind":"company","name":"Exelixis","route":"/companies/exelixis/"}],"person":[{"id":"neeraj-agarwal","kind":"person","name":"Neeraj Agarwal","route":"/people/neeraj-agarwal/"},{"id":"sumanta-pal","kind":"person","name":"Sumanta K. Pal","route":"/people/sumanta-pal/"}],"pairing":[{"id":"io-rechallenge-caution-rcc","kind":"pairing","name":"Caution: PD-1 rechallenge after progression on immunotherapy (RCC)","route":"/pairings/io-rechallenge-caution-rcc/"}]}}