{"entity":{"id":"paper-krystal-1-crc-yaeger-nejm-2023","kind":"paper","name":"KRYSTAL-1: adagrasib with or without cetuximab in KRAS G12C-mutated colorectal cancer","aka":[],"tldr":"The KRAS G12C inhibitor adagrasib on its own shrank about one in five previously treated colorectal cancers, but combined with the EGFR antibody cetuximab the response rate rose to nearly half, showing the two drugs are needed together in this disease.","summary":"Phase 1/2 study including 44 patients with KRAS G12C-mutated metastatic colorectal cancer treated with adagrasib alone and 32 treated with adagrasib plus cetuximab, all heavily pretreated.\n\nObjective response was 19 percent with monotherapy (median progression-free survival 5.6 months) and 46 percent with the combination (median progression-free survival 6.9 months, median overall survival 13.4 months).","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2212419"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36546659/"}],"tags":[],"related":[],"cancers":["kras-g12c-colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":["adagrasib","cetuximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2212419","pmid":"36546659","authors":"Yaeger R, Weiss J, Pelster MS, et al.","paperType":"observational","findings":["Objective response 19 percent with adagrasib alone vs 46 percent with adagrasib plus cetuximab.","Median overall survival 13.4 months with the combination."],"whatItMeans":"Adagrasib plus cetuximab is an approved option for previously treated KRAS G12C colorectal cancer, alongside sotorasib plus panitumumab; monotherapy is not enough because EGFR signalling reactivates the pathway.","caveats":["Small single-arm cohorts.","Responses are shorter than in KRAS G12C lung cancer."],"changedPractice":true,"participants":76},"route":"/key-papers/paper-krystal-1-crc-yaeger-nejm-2023/","neighbours":{"cancer":[{"id":"kras-g12c-colorectal","kind":"cancer","name":"KRAS G12C-mutant colorectal cancer","route":"/cancers/kras-g12c-colorectal/"}],"drug":[{"id":"adagrasib","kind":"drug","name":"Adagrasib","route":"/drugs/adagrasib/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}