{"entity":{"id":"cave","kind":"trial","name":"CAVE mCRC","aka":["CAVE"],"tldr":"Adding a PD-L1 antibody to an EGFR antibody given a second time helped most in patients whose blood showed no resistance mutations, a seven-month difference in survival between the two groups.","summary":"CAVE enrolled 77 patients with pretreated RAS wild-type metastatic colorectal cancer, 71 of them microsatellite-stable, and gave cetuximab rechallenge with avelumab. The trial met its primary endpoint with a median overall survival of 11.6 months (95% CI 8.4 to 14.8) and median progression-free survival of 3.6 months. Baseline circulating tumour DNA for KRAS, NRAS, BRAF and EGFR S492R was analysable in 67 of 77 (87 percent); 48 patients were wild-type in plasma and 19 mutated. Median overall survival was 17.3 months in the plasma wild-type group against 10.4 months in the mutated group (hazard ratio 0.49, 95% CI 0.27 to 0.90, p=0.02), and progression-free survival 4.1 against 3.0 months (hazard ratio 0.42, 0.23 to 0.75, p=0.004). Grade 3 cutaneous eruption affected 14 percent. A later pooled analysis of 180 patients found that the absence of liver metastases and a longer anti-EGFR-free interval mark out who benefits. Like CHRONOS, CAVE is single-arm: it establishes that plasma RAS status selects for rechallenge benefit, not that rechallenge beats standard later-line treatment.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT04561336","url":"https://clinicaltrials.gov/study/NCT04561336"},{"label":"CAVE: cetuximab plus avelumab as rechallenge therapy in RAS wild-type metastatic colorectal cancer (JAMA Oncology 2021)","url":"https://doi.org/10.1001/jamaoncol.2021.2915"},{"label":"CAVE pooled analysis of clinical factors and outcomes (ESMO Gastrointestinal Oncology 2026)","url":"https://doi.org/10.1016/j.esmogo.2026.100398"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["monoclonal-antibody","checkpoint-inhibitor","liquid-biopsy"],"targets":["egfr","pd1"],"drugs":["cetuximab","avelumab"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","msi"],"trials":["chronos"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04561336","phase":"2","setting":"Pretreated RAS wild-type metastatic colorectal cancer: cetuximab rechallenge with the PD-L1 antibody avelumab, single arm","sponsor":"University of Campania Luigi Vanvitelli","result":"Median overall survival 11.6 months overall; 17.3 months with RAS and BRAF wild-type plasma against 10.4 months with mutated plasma (hazard ratio 0.49).","yearReported":2021,"enrolled":77,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Cetuximab rechallenge plus avelumab","n":77,"value":11.6}],"ci":[8.4,14.8],"source":"https://doi.org/10.1001/jamaoncol.2021.2915"},{"endpoint":"Overall survival by baseline plasma RAS and BRAF status","unit":"months","arms":[{"name":"Plasma wild-type","n":48,"value":17.3},{"name":"Plasma mutated","n":19,"value":10.4}],"hr":0.49,"ci":[0.27,0.9],"p":"0.02","source":"https://doi.org/10.1001/jamaoncol.2021.2915"}],"replication":"A 2026 pooled analysis of 180 patients found median overall survival 15.7 months with cetuximab and avelumab against 12.9 months with cetuximab alone, with liver involvement and a short anti-EGFR-free interval marking out non-responders."},"route":"/trials/cave/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"}],"trial":[{"id":"chronos","kind":"trial","name":"CHRONOS","route":"/trials/chronos/"}]}}