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Page 1
KRAS(G12C) Inhibition with Sotorasib in Advanced Solid Tumors.
Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, Bang YJ, Dy GK, Krauss JC, Kuboki Y, Kuo JC, Coveler AL, Park K, Kim TW, Barlesi F, Munster PN, Ramalingam SS, Burns TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G, Kim J, Houk BE, Canon J, Lipford JR, Friberg G, Lito P, Govindan R, Li BT. Hong DS, et al. N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239. Epub 2020 Sep 20. N Engl J Med. 2020. PMID: 32955176 Free PMC article. Clinical Trial.
Sotorasib is a small molecule that selectively and irreversibly targets KRAS(G12C). METHODS: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. ...RESULTS: A total of 129 patients (59 wi …
Sotorasib is a small molecule that selectively and irreversibly targets KRAS(G12C). METHODS: We conducted a phase 1 …
Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C.
Yaeger R, Weiss J, Pelster MS, Spira AI, Barve M, Ou SI, Leal TA, Bekaii-Saab TS, Paweletz CP, Heavey GA, Christensen JG, Velastegui K, Kheoh T, Der-Torossian H, Klempner SJ. Yaeger R, et al. N Engl J Med. 2023 Jan 5;388(1):44-54. doi: 10.1056/NEJMoa2212419. Epub 2022 Dec 21. N Engl J Med. 2023. PMID: 36546659 Free PMC article. Clinical Trial.
BACKGROUND: Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. ...CONCLUSIONS: Adagrasib had antitumor activity in heavily p …
BACKGROUND: Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated …
Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation.
Sacher A, LoRusso P, Patel MR, Miller WH Jr, Garralda E, Forster MD, Santoro A, Falcon A, Kim TW, Paz-Ares L, Bowyer S, de Miguel M, Han SW, Krebs MG, Lee JS, Cheng ML, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin MT, Royer-Joo S, Chang J, Dharia NV, Schutzman JL, Desai J; GO42144 Investigator and Study Group. Sacher A, et al. N Engl J Med. 2023 Aug 24;389(8):710-721. doi: 10.1056/NEJMoa2303810. N Engl J Med. 2023. PMID: 37611121 Free article. Clinical Trial.
BACKGROUND: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity. METHODS: In a phase 1 study, we evaluated divarasib administered orally once daily (at doses ranging from 50 to 400 mg) in patien …
BACKGROUND: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity. MET …
D3S-001 in advanced solid tumors with KRAS(G12C) mutations: a phase 1 trial.
Cho BC, Lu S, Lee MA, Song Z, Park JJ, Lim SM, Li Z, Zhao J, Richardson G, Zhang Y, Zhang J, Liu A, Loong HH, Chen C, Wang J, Shen Y, Fan Z, Chen Q, Wang H, Zhang J, Chen ZJ, Johnson ML, Mok T. Cho BC, et al. Nat Med. 2025 Aug;31(8):2768-2777. doi: 10.1038/s41591-025-03688-6. Epub 2025 Apr 29. Nat Med. 2025. PMID: 40301557 Clinical Trial.
D3S-001 is a next-generation KRAS-G12C inhibitor (G12Ci) designed to enhance target engagement efficiency and overcome growth factor-induced nucleotide exchange. ...Confirmed ORR in the G12Ci-naive population was 73.5% overall (25 of 34), and 66.7% (14 of 21), 88.9% …
D3S-001 is a next-generation KRAS-G12C inhibitor (G12Ci) designed to enhance target engagement efficiency and overcome growth …
Targeting KRAS in Colorectal Cancer.
Wang C, Fakih M. Wang C, et al. Curr Oncol Rep. 2021 Feb 13;23(3):28. doi: 10.1007/s11912-021-01022-0. Curr Oncol Rep. 2021. PMID: 33582927 Review.
RECENT FINDINGS: KRAS(G12C) mutation was found in 14% of non-small cell lung cancer (NSCLC) and 3% of colorectal cancer. ...Early results from phase 1 clinical trials with sotorasib and MRTX849 show promising antitumor activity in NSCLC, …
RECENT FINDINGS: KRAS(G12C) mutation was found in 14% of non-small cell lung cancer (NSCLC) and 3% of colorectal can …
Glecirasib with or without cetuximab in previously treated locally advanced or metastatic colorectal cancer with KRAS(G12C) mutation (JAB-21822-1002 and JAB-21822-1007): two open-label, non-randomised phase 1/2 trials.
Li J, Wang Z, Huang J, Ba Y, Cao B, Luo S, Li W, Bai C, Song Z, Xiong J, Zhu L, An G, Zhang Y, Li Z, Li Y, Gu Y, Hu C, Li X, Huang C, Fu Q, Yin X, Liang X, Zhong D, Shi H, Li X, Li Z, Liu L, Wang F, Liang R, Xia G, Wang Z, Wang-Gillam A, Ding Y, Rao Z, Pan W, Lu S, Sun X, Shen L. Li J, et al. Lancet Gastroenterol Hepatol. 2026 Feb;11(2):110-123. doi: 10.1016/S2468-1253(25)00267-5. Epub 2025 Dec 1. Lancet Gastroenterol Hepatol. 2026. PMID: 41344351 Clinical Trial.
BACKGROUND: KRAS(G12C) mutations are present in around 4% of patients with colorectal cancer and are associated with lower treatment response rates and overall survival. EGFR signalling has been identified as a primary mechanism of resistance to KRA …
BACKGROUND: KRAS(G12C) mutations are present in around 4% of patients with colorectal cancer and are associated …
Sotorasib for previously treated colorectal cancers with KRAS(G12C) mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial.
Fakih MG, Kopetz S, Kuboki Y, Kim TW, Munster PN, Krauss JC, Falchook GS, Han SW, Heinemann V, Muro K, Strickler JH, Hong DS, Denlinger CS, Girotto G, Lee MA, Henary H, Tran Q, Park JK, Ngarmchamnanrith G, Prenen H, Price TJ. Fakih MG, et al. Lancet Oncol. 2022 Jan;23(1):115-124. doi: 10.1016/S1470-2045(21)00605-7. Epub 2021 Dec 15. Lancet Oncol. 2022. PMID: 34919824 Clinical Trial.
BACKGROUND: Sotorasib, a specific, irreversible KRAS(G12C) protein inhibitor, has shown monotherapy clinical activity in KRAS(G12C)-mutated solid tumours, including colorectal cancer, in the CodeBreaK100 phase 1 trial. ...Th …
BACKGROUND: Sotorasib, a specific, irreversible KRAS(G12C) protein inhibitor, has shown monotherapy clinical activity in KR …
Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors.
Choi Y, Dharia NV, Jun T, Chang J, Royer-Joo S, Yau KK, Assaf ZJ, Aimi J, Sivakumar S, Montesion M, Sacher A, LoRusso P, Desai J, Schutzman JL, Shi Z; and the GO42144 study group. Choi Y, et al. Clin Cancer Res. 2024 Sep 3;30(17):3788-3797. doi: 10.1158/1078-0432.CCR-24-0255. Clin Cancer Res. 2024. PMID: 38995268 Free PMC article. Clinical Trial.
PURPOSE: To inform prognosis, treatment response, disease biology, and KRAS G12C mutation heterogeneity, we conducted exploratory circulating tumor DNA (ctDNA) profiling on 134 patients with solid tumors harboring a KRAS G12C mutation treated with sing …
PURPOSE: To inform prognosis, treatment response, disease biology, and KRAS G12C mutation heterogeneity, we conducted explorat …
Editorial: Recent Approval of Sotorasib as the First Targeted Therapy for KRAS G12C-Mutated Advanced Non-Small Cell Lung Cancer (NSCLC).
Parums DV. Parums DV. Med Sci Monit. 2022 Nov 1;28:e938746. doi: 10.12659/MSM.938746. Med Sci Monit. 2022. PMID: 36317327 Free PMC article.
The main KRAS mutations are single-base missense mutations, with 98% occurring at codon 12 (G12C). KRAS G12C is the most common KRAS mutation in NSCLC. Sotorasib is a first-in-class specific small molecule that irreversibly inhibits KRAS G12C. B …
The main KRAS mutations are single-base missense mutations, with 98% occurring at codon 12 (G12C). KRAS G12C is the mos …
A case of adenosquamous pancreatic cancer with a KRAS G12C mutation with an exceptional response to immunotherapy.
Ahmed M, Larson BK, Osipov A, Azad N, Hendifar A. Ahmed M, et al. Oncotarget. 2024 Oct 11;15:741-747. doi: 10.18632/oncotarget.28659. Oncotarget. 2024. PMID: 39392392 Free PMC article.
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths, with adenosquamous carcinoma of the pancreas (ASCP), a rare variant, representing 1-10% of cases. ...This report describes a 68-year-old male with metastatic ASCP and a KR …
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths, with adenosquamous carcinoma of th …