{"entity":{"id":"krystal-12","kind":"trial","name":"KRYSTAL-12","aka":[],"tldr":"Confirmed that the KRAS pill adagrasib beats chemotherapy after first-line treatment, though the gain is modest.","summary":"KRYSTAL-12, trial NCT04685135 sponsored by Bristol Myers Squibb through Mirati and reported in 2024, confirmed that the KRAS G12C inhibitor adagrasib beats docetaxel after first-line treatment in KRAS G12C-mutant non-small-cell lung cancer, though the gain is modest. It randomised 453 patients, met its primary progression-free survival endpoint by blinded review and showed higher objective and intracranial response rates than chemotherapy, supporting full approval and the second-line role of G12C inhibitors, while overall survival was not yet significantly different. OnCo links it to KRAS as a target and to the bottleneck of undruggable drivers, and its result is consistent with CodeBreaK 200 for sotorasib, where neither trial showed a survival benefit. Whether G12C inhibitors help more in first-line combinations is the open question. Adagrasib has its own page.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT04685135","url":"https://clinicaltrials.gov/study/NCT04685135"}],"tags":[],"related":[],"cancers":["nsclc","kras-g12c-nsclc"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["adagrasib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-krystal-12-plain-language-summary-future-oncol-2026"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04685135","phase":"3","setting":"Previously treated KRAS G12C NSCLC: adagrasib vs docetaxel","sponsor":"BMS (Mirati)","result":"PFS HR 0.58.","started":"2021-02-23","startedType":"actual","yearReported":2024,"enrolled":453,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (BICR)","primary":true,"unit":"months","arms":[{"name":"Adagrasib","n":301,"value":5.5},{"name":"Docetaxel","n":152,"value":3.8}],"hr":0.58,"ci":[0.45,0.76],"p":"<0.0001","source":"https://clinicaltrials.gov/study/NCT04685135"}],"replication":"Consistent with CodeBreaK 200 (sotorasib vs docetaxel, PFS HR 0.66); neither trial showed an OS benefit."},"route":"/trials/krystal-12/","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":"adagrasib","kind":"drug","name":"Adagrasib","route":"/drugs/adagrasib/"}],"paper":[{"id":"paper-krystal-12-plain-language-summary-future-oncol-2026","kind":"paper","name":"KRYSTAL-12 plain language summary: adagrasib for non-small-cell lung cancer with KRAS G12C mutations","route":"/key-papers/paper-krystal-12-plain-language-summary-future-oncol-2026/"}],"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/"}]}}