{"entity":{"id":"paper-krystal-1-adagrasib-kras-g12c-solid-tumours-jco-2023","kind":"paper","name":"KRYSTAL-1: adagrasib in advanced solid tumours harbouring a KRAS G12C mutation, including pancreatic cancer","aka":[],"tldr":"Adagrasib, the second KRAS G12C pill, shrank tumours in about a third of patients with pancreatic cancer and in two in five with bile duct cancer in this basket study, with disease control for several months.","summary":"Phase 2 cohort of the KRYSTAL-1 trial in 64 patients with previously treated KRAS G12C-mutated solid tumours other than lung or colorectal cancer, treated with adagrasib 600 mg twice daily. The pancreatic cohort had 21 patients and the biliary tract cohort 12; other tumours included appendiceal, ovarian, endometrial and small bowel cancers.\n\nIn pancreatic cancer the objective response rate was about 33 percent, with median progression-free survival of 5.4 months and median overall survival of 8.0 months; in biliary tract cancer the response rate was about 42 percent. Treatment-related adverse events were mostly gastrointestinal and manageable with dose reduction.","asOf":"2026-09-21","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/JCO.23.00434"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37099736/"}],"tags":[],"related":[],"cancers":["kras-g12c-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["adagrasib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03785249"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.23.00434","pmid":"37099736","authors":"Bekaii-Saab TS, Yaeger R, Spira AI, et al.","paperType":"observational","findings":["Pancreatic cohort (21 patients): objective response about 33 percent, median progression-free survival 5.4 months, median overall survival 8.0 months.","Biliary tract cohort (12 patients): objective response about 42 percent."],"whatItMeans":"Adagrasib joins sotorasib as a later-line option for KRAS G12C pancreatic cancer in guidelines; both drugs are the template for the G12D and pan-RAS inhibitors now in pancreatic trials.","caveats":["Small single-arm cohorts with a short follow-up; the pancreatic response rate has a wide confidence interval.","KRAS G12C is found in only 1 to 2 percent of pancreatic cancers."],"changedPractice":true,"participants":64},"route":"/key-papers/paper-krystal-1-adagrasib-kras-g12c-solid-tumours-jco-2023/","neighbours":{"cancer":[{"id":"kras-g12c-pdac","kind":"cancer","name":"KRAS G12C-mutant pancreatic ductal adenocarcinoma","route":"/cancers/kras-g12c-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"drug":[{"id":"adagrasib","kind":"drug","name":"Adagrasib","route":"/drugs/adagrasib/"}],"trial":[{"id":"nct03785249","kind":"trial","name":"Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1","route":"/trials/nct03785249/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}