{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T05:56:52Z","timestamp":1793858212133,"version":"4.6.1"},"reference-count":39,"publisher":"American Association for Cancer Research (AACR)","issue":"6","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":56,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016957","name":"Mirati Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Adagrasib, an irreversible, selective KRASG12C inhibitor, may be an effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients with previously treated KRASG12C-mutated unresectable or metastatic colorectal cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review. Ninety-four patients received adagrasib plus cetuximab. With a median follow-up of 11.9 months, ORR was 34.0%, disease control rate was 85.1%, and median duration of response was 5.8 months (95% confidence interval [CI], 4.2\u20137.6). Median progression-free survival was 6.9 months (95% CI, 5.7\u20137.4) and median overall survival was 15.9 months (95% CI, 11.8\u201318.8). Treatment-related adverse events (TRAEs) occurred in all patients; grade 3\u20134 in 27.7% and no grade 5. No TRAEs led to adagrasib discontinuation. Exploratory analyses suggest circulating tumor DNA may identify features of response and acquired resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or metastatic KRASG12C-mutated colorectal cancer. These data support a potential new standard of care and highlight the significance of testing and identification of KRASG12C mutations in patients with colorectal cancer.<\/jats:p>\n                    <jats:p>This article is featured in Selected Articles from This Issue, p. 897<\/jats:p>\n                    <jats:p>See co-corresponding author Rona Yaeger discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https:\/\/vimeo.com\/932606282\/f27a6e46f4<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-24-0217","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T11:29:17Z","timestamp":1712575757000},"page":"982-993","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":149,"title":["Efficacy and Safety of Adagrasib plus Cetuximab in Patients with\n                    <i>KRAS<\/i>\n                    G12C-Mutated Metastatic Colorectal Cancer"],"prefix":"10.1158","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7233-5454","authenticated-orcid":false,"given":"Rona","family":"Yaeger","sequence":"first","affiliation":[{"name":"1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3449-1680","authenticated-orcid":false,"given":"Nataliya V.","family":"Uboha","sequence":"additional","affiliation":[{"name":"2Division of Hematology and Oncology, Department of Medicine, University of Wisconsin, Madison, Wisconsin."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2448-3478","authenticated-orcid":false,"given":"Meredith S.","family":"Pelster","sequence":"additional","affiliation":[{"name":"3Sarah Cannon Research Institute, Tennessee Oncology, Nashville, Tennessee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-1699","authenticated-orcid":false,"given":"Tanios S.","family":"Bekaii-Saab","sequence":"additional","affiliation":[{"name":"4Department of Medical Oncology and Hematology, Mayo Clinic, Scottsdale, Arizona."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4259-7457","authenticated-orcid":false,"given":"Minal","family":"Barve","sequence":"additional","affiliation":[{"name":"5Mary Crowley Cancer Research Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1869-9887","authenticated-orcid":false,"given":"Joel","family":"Saltzman","sequence":"additional","affiliation":[{"name":"6Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1556-1543","authenticated-orcid":false,"given":"Joshua K.","family":"Sabari","sequence":"additional","affiliation":[{"name":"7Division of Medical Oncology, Perlmutter Cancer Center, New York University Langone Health, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9464-4901","authenticated-orcid":false,"given":"Julio A.","family":"Peguero","sequence":"additional","affiliation":[{"name":"8Department of Research, Oncology Consultants PA, Houston, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6023-670X","authenticated-orcid":false,"given":"Andrew Scott","family":"Paulson","sequence":"additional","affiliation":[{"name":"9Department of Medical Oncology, Texas Oncology \u2013 Baylor Charles A. Sammons Cancer Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7821-4928","authenticated-orcid":false,"given":"Pasi A.","family":"J\u00e4nne","sequence":"additional","affiliation":[{"name":"10Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8147-7457","authenticated-orcid":false,"given":"Marcia","family":"Cruz-Correa","sequence":"additional","affiliation":[{"name":"11PanOncology Trials, San Juan, Puerto Rico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4515-2011","authenticated-orcid":false,"given":"Kenna","family":"Anderes","sequence":"additional","affiliation":[{"name":"12Mirati Therapeutics, a wholly owned subsidiary of Bristol Myers Squibb Company, San Diego, 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