{"entity":{"id":"chronos","kind":"trial","name":"CHRONOS","aka":[],"tldr":"The first trial to let a blood test decide whether to give an EGFR antibody a second time. A third of the patients screened had resistance mutations and were excluded; of those rechallenged, three in ten responded.","summary":"Resistance to EGFR antibodies in colorectal cancer arises through RAS, BRAF and EGFR ectodomain mutant clones that expand under treatment and then decline once the drug is withdrawn, which raises the possibility of rechallenging the same tumour later. CHRONOS was an open-label, single-arm phase 2 trial that tested this prospectively: patients whose tissue was RAS wild-type and who had already progressed on an EGFR-based regimen had an interventional circulating tumour DNA screen, and only those without a detectable RAS, BRAF or EGFR resistance mutation were rechallenged with chemotherapy-free panitumumab. Of 52 patients screened, 16 (31 percent) carried at least one resistance mutation and were excluded. Of the 27 enrolled, eight (30 percent) achieved a partial response, including two unconfirmed responses, and 17 (63 percent) had disease control. The primary endpoint was met. These figures compare favourably with standard third-line treatment, and CHRONOS is the proof that a liquid biopsy can be used interventionally, to choose treatment rather than to describe a tumour. It is small and single-arm, so anti-EGFR rechallenge remains unproven in phase 3.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT03227926","url":"https://clinicaltrials.gov/study/NCT03227926"},{"label":"CHRONOS: ctDNA-guided anti-EGFR rechallenge with panitumumab in metastatic colorectal cancer (Nature Medicine 2022)","url":"https://doi.org/10.1038/s41591-022-01886-0"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["liquid-biopsy","monoclonal-antibody","mrd-testing"],"targets":["egfr","kras","nras","braf"],"drugs":["panitumumab"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03227926","phase":"2","setting":"RAS wild-type metastatic colorectal cancer that had already progressed on an EGFR antibody: a blood test for RAS, BRAF and EGFR resistance mutations decides who is rechallenged with panitumumab alone","sponsor":"Fondazione del Piemonte per l'Oncologia","result":"Objective response 30 percent (8 of 27) and disease control 63 percent in ctDNA-selected patients; 31 percent of those screened were excluded by a resistance mutation.","yearReported":2022,"enrolled":27,"enrolledBasis":"treated","enrolledNote":"The registry lists 32 participants; 52 patients underwent the interventional circulating tumour DNA screen, 16 (31 percent) were excluded for a resistance mutation and 27 were enrolled and treated.","outcomes":[{"endpoint":"Objective response rate","primary":true,"unit":"percent","arms":[{"name":"Panitumumab rechallenge after a negative ctDNA resistance screen","n":27,"value":30,"note":"8 of 27, including 2 unconfirmed"}],"source":"https://doi.org/10.1038/s41591-022-01886-0"}]},"route":"/trials/chronos/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"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/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"nras","kind":"target","name":"NRAS","route":"/targets/nras/"}],"drug":[{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"}],"trial":[{"id":"cave","kind":"trial","name":"CAVE mCRC","route":"/trials/cave/"}]}}