{"entity":{"id":"codebreak-200","kind":"trial","name":"CodeBreaK 200","aka":[],"tldr":"The first randomised trial of a KRAS drug: better than chemotherapy on progression, not on survival.","summary":"CodeBreaK 200, trial NCT04303780 sponsored by Amgen and reported in 2022, was the first randomised trial of a KRAS drug, comparing sotorasib with docetaxel in previously treated KRAS G12C-mutant non-small-cell lung cancer. It randomised 345 patients, met its primary progression-free survival endpoint by blinded review and showed a higher response rate, but overall survival was no different, a result confounded by crossover and dropout, and an FDA advisory committee questioned the benefit in 2023 so that full approval was not granted on this trial alone. OnCo links it to KRAS as a target, to Ferdinandos Skoulidis and to the bottleneck of undruggable drivers, and its findings are consistent with KRYSTAL-12 for adagrasib. Whether a progression benefit without a survival benefit justifies a new standard is the question the trial forced the field to confront. Sotorasib has its own page.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT04303780","url":"https://clinicaltrials.gov/study/NCT04303780"}],"tags":[],"related":[],"cancers":["nsclc","kras-g12c-nsclc"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["sotorasib"],"companies":["amgen"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["ferdinandos-skoulidis"],"bottlenecks":[],"keyPapers":["paper-codebreak-200-lancet-2023"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04303780","phase":"3","setting":"Previously treated KRAS G12C NSCLC: sotorasib vs docetaxel","sponsor":"Amgen","result":"PFS HR 0.66; OS HR 1.01.","started":"2020-06-04","startedType":"actual","yearReported":2022,"enrolled":345,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (BICR)","primary":true,"unit":"months","arms":[{"name":"Sotorasib","n":171,"value":5.6},{"name":"Docetaxel","n":174,"value":4.5}],"hr":0.66,"ci":[0.51,0.86],"p":"0.0017","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00221-0/fulltext"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Sotorasib","value":10.6,"note":"Not significant; crossover permitted"},{"name":"Docetaxel","value":11.3}],"hr":1.01,"source":"https://doi.org/10.1016/S0140-6736(23)00221-0"}],"replication":"Consistent with KRYSTAL-12 (adagrasib) on PFS; the FDA declined full approval at the 960 mg dose pending further data."},"route":"/trials/codebreak-200/","neighbours":{"cancer":[{"id":"kras-g12c-nsclc","kind":"cancer","name":"KRAS G12C-mutant non-small-cell lung cancer","route":"/cancers/kras-g12c-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"drug":[{"id":"sotorasib","kind":"drug","name":"Sotorasib","route":"/drugs/sotorasib/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}],"person":[{"id":"ferdinandos-skoulidis","kind":"person","name":"Ferdinandos Skoulidis","route":"/people/ferdinandos-skoulidis/"}],"paper":[{"id":"paper-codebreak-200-lancet-2023","kind":"paper","name":"CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug","route":"/key-papers/paper-codebreak-200-lancet-2023/"}],"term":[{"id":"crossover","kind":"term","name":"Crossover in trials","route":"/terms/crossover/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"},{"id":"surrogate-validation","kind":"term","name":"Surrogate endpoint validation: which stand-ins have earned trust","route":"/terms/surrogate-validation/"},{"id":"trial-failure-modes","kind":"term","name":"Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover","route":"/terms/trial-failure-modes/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}