{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:38:54Z","timestamp":1792219134467,"version":"4.4.0"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"25","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Adagrasib, a KRAS\n                      <jats:sup>G12C<\/jats:sup>\n                      inhibitor, has demonstrated clinical activity in patients with KRAS\n                      <jats:sup>G12C<\/jats:sup>\n                      -mutated non\u2013small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRAS\n                      <jats:sup>G12C<\/jats:sup>\n                      mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRAS\n                      <jats:sup>G12C<\/jats:sup>\n                      mutation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249 ; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRAS\n                      <jats:sup>G12C<\/jats:sup>\n                      -mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival (PFS), overall survival, and safety.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      As of October 1, 2022, 64 patients with KRAS\n                      <jats:sup>G12C<\/jats:sup>\n                      -mutated solid tumors were enrolled and 63 patients treated (median follow-up, 16.8 months). The median number of prior lines of systemic therapy was 2. Among 57 patients with measurable disease at baseline, objective responses were observed in 20 (35.1%) patients (all partial responses), including 7\/21 (33.3%) responses in pancreatic and 5\/12 (41.7%) in biliary tract cancers. The median duration of response was 5.3 months (95% CI, 2.8 to 7.3) and median PFS was 7.4 months (95% CI, 5.3 to 8.6). Treatment-related adverse events (TRAEs) of any grade were observed in 96.8% of patients and grade 3-4 in 27.0%; there were no grade 5 TRAEs. TRAEs did not lead to treatment discontinuation in any patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Adagrasib demonstrates encouraging clinical activity and is well tolerated in this rare cohort of pretreated patients with KRAS\n                      <jats:sup>G12C<\/jats:sup>\n                      -mutated solid tumors.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.23.00434","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T15:59:05Z","timestamp":1682524745000},"page":"4097-4106","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":310,"title":["Adagrasib in Advanced Solid Tumors Harboring a\n                    <i>KRAS<\/i>\n                    <sup>\n                      <i>G12C<\/i>\n                    <\/sup>\n                    Mutation"],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct03785249","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-1699","authenticated-orcid":true,"given":"Tanios S.","family":"Bekaii-Saab","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Hematology, Mayo Clinic, Scottsdale, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7233-5454","authenticated-orcid":true,"given":"Rona","family":"Yaeger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1303-0447","authenticated-orcid":true,"given":"Alexander I.","family":"Spira","sequence":"additional","affiliation":[{"name":"Virginia Cancer Specialists, Fairfax, 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