Abstract 437TiP
Background
Sotorasib selectively and irreversibly inhibits the Kirsten rat sarcoma (KRAS) G12C mutant protein. This inhibition can result in accumulation of activated epidermal growth factor receptor (EGFR), which may drive resistance to sotorasib. Therefore, the combination of sotorasib with an EGFR inhibitor, such as panitumumab, might lead to more complete inhibition of tumor cell growth and survival. Early data for the combination of sotorasib and panitumumab from CodeBreaK 101 subprotocol H showed promising antitumor activity in chemorefractory metastatic colorectal cancer (mCRC). The objective of the current study is to evaluate whether the combination of sotorasib and panitumumab is superior to standard of care trifluridine/tipiracil or regorafenib in the setting of chemorefractory mCRC.
Trial design
CodeBreaK 300 (NCT05198934) is a global phase III randomized, open-label, active-controlled study of the efficacy and safety of oral sotorasib combined with intravenous panitumumab in patients with mCRC. Key eligibility criteria include mCRC with KRAS G12C mutation confirmed by central molecular testing of tumor biopsy, and at least 1 prior line of therapy. Patients must have received and progressed or experienced disease recurrence on or after fluoropyrimidine, irinotecan, and oxaliplatin given for metastatic disease unless ineligible in the opinion of the investigator. Approximately 153 patients will be enrolled and randomized 1:1:1 to receive either sotorasib 960 mg daily and panitumumab or sotorasib 240 mg daily and panitumumab or investigator’s choice (trifluridine and tipiracil, or regorafenib). The primary endpoint is progression-free survival using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR). Key secondary endpoints include overall survival and objective response. Global enrollment is ongoing.
Clinical trial identification
NCT05198934.
Editorial acknowledgement
Medical writing support was provided by Tim Harrison, PharmD (Amgen Inc.).
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
D. Paez: Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Other, Consulting fees: Amgen, Ipsen, Servier; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, Sanofi, AAA; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Amgen, Merck, Roche, Lilly, Servier, Sanofi, Ipsen. C. Cremolini: Financial Interests, Personal, Other, Honoraria/Consultant: Amgen, Bayer, Merck, MSD, Nordic Pharma, Organon, Pierre Fabre, Roche, Servier; Financial Interests, Personal, Research Grant: Bayer, Merck, Servier. G. Folprecht: Financial Interests, Personal, Invited Speaker: Roche / Genentech, Falk Foundation, Lilly; Financial Interests, Personal, Advisory Board: Sanofi-Aventis, Merck, BMS, MSD, Servier, Pierre Fabre, Roche / Genentech, Bayer, Exact Sciences. I. Korantzis: Financial Interests, Personal, Other, Honoraria and Advisory board member: Boehringer Ingelheim, Sandoz, Amgen, Roche; Financial Interests, Personal, Other, Sponsored lecture: AstraZeneca, Pfizer, Novartis, Roche, Sanofi, MSD, Merck, Amgen, BMS. E. Chan: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. Q. Tran: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. M.G. Fakih: Financial Interests, Institutional, Research Grant: Genentech, Verastem; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Bayer Corporation, HalioDX, Incyte Corporation, Mirati, Pfizer, Inc., PsiOxus, Taiho Oncology, Zhuhai Yufan Biotech; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, Inc., Guardant360; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Amgen, Inc., Bayer Corporation, GlaxoSmithKline, Nouscom, Roche/Genentech, Seattle Genetics; Financial Interests, Institutional, Other, Study-related drugs supplied to institution: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.