A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)

Summary

Evaluate the safety and tolerability of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors. Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with KRAS p.G12C mutant advanced solid tumors.

Timeline

Start

2018-08-27

Primary completion

2026-05-29

Completion

2026-05-29

Publications

• Background Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30.
• Background Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V, Govindan R. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 Jun 24;384(25):2371-2381. doi: 10.1056/NEJMoa2103695. Epub 2021 Jun 4.
• Background 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. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol. 2022 Jan;23(1):115-124. doi: 10.1016/S1470-2045(21)00605-7. Epub 2021 Dec 15.
• Background 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. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239. Epub 2020 Sep 20.
• Background Zhao Y, Murciano-Goroff YR, Xue JY, Ang A, Lucas J, Mai TT, Da Cruz Paula AF, Saiki AY, Mohn D, Achanta P, Sisk AE, Arora KS, Roy RS, Kim D, Li C, Lim LP, Li M, Bahr A, Loomis BR, de Stanchina E, Reis-Filho JS, Weigelt B, Berger M, Riely G, Arbour KC, Lipford JR, Li BT, Lito P. Diverse alterations associated with resistance to KRAS(G12C) inhibition. Nature. 2021 Nov;599(7886):679-683. doi: 10.1038/s41586-021-04065-2. Epub 2021 Nov 10.
• Background Dy GK, Govindan R, Velcheti V, Falchook GS, Italiano A, Wolf J, Sacher AG, Takahashi T, Ramalingam SS, Dooms C, Kim DW, Addeo A, Desai J, Schuler M, Tomasini P, Hong DS, Lito P, Tran Q, Jones S, Anderson A, Hindoyan A, Snyder W, Skoulidis F, Li BT. Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100. J Clin Oncol. 2023 Jun 20;41(18):3311-3317. doi: 10.1200/JCO.22.02524. Epub 2023 Apr 25.
• Background Dy GK, Govindan R, Velcheti V, Falchook GS, Italiano A, Wolf J, Sacher AG, Takahashi T, Ramalingam SS, Dooms C, Kim DW, Addeo A, Desai J, Schuler M, Tomasini P, Hong DS, Lito P, Tran Q, Jones S, Anderson A, Hindoyan A, Snyder W, Skoulidis F, Li BT. Long-term benefit of sotorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: plain language summary. Future Oncol. 2024 Jan;20(3):113-120. doi: 10.2217/fon-2023-0560. Epub 2023 Nov 27.
• Background Dilly J, Hoffman MT, Abbassi L, Li Z, Paradiso F, Parent BD, Hennessey CJ, Jordan AC, Morgado M, Dasgupta S, Uribe GA, Yang A, Kapner KS, Hambitzer FP, Qiang L, Feng H, Geisberg J, Wang J, Evans KE, Lyu H, Schalck A, Feng N, Lopez AM, Bristow CA, Kim MP, Rajapakshe KI, Bahrambeigi V, Roth JA, Garg K, Guerrero PA, Stanger BZ, Cristea S, Lowe SW, Baslan T, Van Allen EM, Mancias JD, Chan E, Anderson A, Katlinskaya YV, Shalek AK, Hong DS, Pant S, Hallin J, Anderes K, Olson P, Heffernan TP, Chugh S, Christensen JG, Maitra A, Wolpin BM, Raghavan S, Nowak JA, Winter PS, Dougan SK, Aguirre AJ. Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer. Cancer Discov. 2024 Nov 1;14(11):2135-2161. doi: 10.1158/2159-8290.CD-24-0177.
• Background Hochmair MJ, Vermaelen K, Mountzios G, Carcereny E, Dooms C, Lee SH, Morocz E, Kato T, Ciuleanu TE, Dy GK, Parente B, O'Byrne KJ, Chu QS, Castro Junior G, Girard N, Snyder W, Tran Q, Kormany W, Houk B, Mehta B, Curioni-Fontecedro A. Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC. Eur J Cancer. 2024 Sep;208:114204. doi: 10.1016/j.ejca.2024.114204. Epub 2024 Jul 5.
• Background Nagase M, Houk B, Vuu I, Cardona P, Dutta S, Lin CW. Population Pharmacokinetics of Sotorasib in Healthy Subjects and Advanced Solid Tumor Patients Harboring a KRASG12C Mutation from Phase 1 and Phase 2 Studies. AAPS J. 2025 Jan 13;27(1):26. doi: 10.1208/s12248-024-01013-6.
• Strickler JH, Satake H, George TJ, Yaeger R, Hollebecque A, Garrido-Laguna I, Schuler M, Burns TF, Coveler AL, Falchook GS, Vincent M, Sunakawa Y, Dahan L, Bajor D, Rha SY, Lemech C, Juric D, Rehn M, Ngarmchamnanrith G, Jafarinasabian P, Tran Q, Hong DS. Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer. N Engl J Med. 2023 Jan 5;388(1):33-43. doi: 10.1056/NEJMoa2208470. Epub 2022 Dec 21.
• Lanman BA, Allen JR, Allen JG, Amegadzie AK, Ashton KS, Booker SK, Chen JJ, Chen N, Frohn MJ, Goodman G, Kopecky DJ, Liu L, Lopez P, Low JD, Ma V, Minatti AE, Nguyen TT, Nishimura N, Pickrell AJ, Reed AB, Shin Y, Siegmund AC, Tamayo NA, Tegley CM, Walton MC, Wang HL, Wurz RP, Xue M, Yang KC, Achanta P, Bartberger MD, Canon J, Hollis LS, McCarter JD, Mohr C, Rex K, Saiki AY, San Miguel T, Volak LP, Wang KH, Whittington DA, Zech SG, Lipford JR, Cee VJ. Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors. J Med Chem. 2020 Jan 9;63(1):52-65. doi: 10.1021/acs.jmedchem.9b01180. Epub 2019 Dec 24.

Drugs

Indications

No indication recorded.