Abstract 444TiP
Background
The oncogenic KRAS G12C mutation is present in about 3% of patients with colorectal cancer (CRC). Sotorasib, a small molecule that specifically and irreversibly inhibits the KRASG12C mutant protein, has demonstrated modest clinical activity and no dose-limiting toxicities as monotherapy in heavily pretreated patients with KRAS G12C-mutated CRC. Inhibition of KRASG12C can result in accumulation of activated epithelial growth factor receptor (EGFR) which may drive resistance to sotorasib. The combination of sotorasib with EGFR inhibitors, such as panitumumab, may enhance antitumor efficacy and counteract potential escape mechanisms. A subprotocol of the CodeBreaK 101 study includes cohorts of patients with metastatic CRC (mCRC) in which the combination of sotorasib with panitumumab plus chemotherapy is being evaluated.
Trial design
The CodeBreaK 101 (NCT04185883) master protocol is a phase Ib open-label study of the safety, tolerability, pharmacokinetics (PK), and efficacy of multiple sotorasib-based combinations in patients with KRAS G12C-mutated advanced solid tumors. Subprotocol H includes dose exploration and expansion in various cohorts, two of which are evaluating oral sotorasib combined with intravenous panitumumab plus FOLFIRI in patients with mCRC: a cohort of patients not previously treated for metastatic disease and another cohort of patients who have received at least one prior therapy for metastatic disease. Key eligibility criteria include mCRC with KRAS G12C mutation. The primary endpoint is safety including dose-limiting toxicities and treatment-emergent or treatment-related adverse events. Secondary endpoints include efficacy (objective response, disease control rate, duration of response, time to response, progression-free survival, and overall survival) and PK parameters. Global enrollment is ongoing. FOLFIRI=5-fluorouracil + leucovorin + irinotecan.
Clinical trial identification
NCT04185883.
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
T. Masuishi: Financial Interests, Institutional, Research Grant: MSD, Daiichi Sankyo, Ono, Novartis, Amgen, Syneos Healthe Clinical, Boehringer Ingelheim, Pfizer, Cimic Shift Zero, Eli Lilly; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Takeda, Chugai, Merck Bio Pharma, Taiho, Bayer, Lilly Japan, Yakult Honsha, Sanofi, Daiichi Sankyo, Ono, Bristol-Myers Squibb. Y. Kuboki: Financial Interests, Institutional, Writing Engagements: Amgen; Financial Interests, Institutional, Research Grant: Taiho, Astellas, Lilly, Takeda, Daiichi-Sankyo, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, GlaxoSmithKline, Incyte, AbbVie; Financial Interests, Personal, Other, Consulting fees: Taiho, Boehringer Ingelheim, Amgen, Takeda; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Taiho, Ono, Lilly, Bristol-Myers Squibb. 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 my institution: Bristol-Myers Squibb. J.H. Strickler: Financial Interests, Personal, Advisory Board: SeaGen, AstraZenca, Amgen, Pfizer, Bayer, AbbVie, Natera, Viatris, Inivata, Silverback Therapeutics; Financial Interests, Personal, Other, Consulting: Mereo, GSK, Pionyr Immunotherapeutics; Financial Interests, Institutional, Invited Speaker: SeaGen, Roche Genentech, AbbVie, AstraZeneca, Amgen, AStar D3, Sanofi, Curegenix, Nektar, Leap Therapeutics, Daiichi Sankyo, Erasca, Gossamer Bio, Silverback Therapeutics. M. Furqan: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Beigene, Mirati, AbbVie; Financial Interests, Institutional, Research Grant: Novartis, Merck, AbbVie, AstraZeneca, Celgene, Genentech, Genmab, Elicio, Inbrx, Mirati, Amgen, GSK, Beigene. E.J. Kim: Financial Interests, Institutional, Research Grant: NGM, Erytech, Fibrogen, Eureka, Merck, BMS, Astellas, Boston Biomedical, AZ, Celgene, Halozyme, Samumed, Epicentrx; Financial Interests, Personal, Other, Consulting fees: Eisai, Taiho, Celgene, Lilly; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Lilly. P. Cardona: 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. E. Chan: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. D.S. Hong: Financial Interests, Personal, Other, Consultancy role: Amgen; Financial Interests, Institutional, Research Grant: Amgen, AbbVie, Adaptimmune, Adlai-Nortye, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Deciphera, Eisai, Endeavor, Erasca, F. Hoffmann-La Roche, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa Kirin, Lilly, LOXO, Merck, Medimmune, Mirati, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, SeaGen, Takeda, TCR2, Teckro, Turning Point Therapeutics, VM Oncology; Financial Interests, Personal, Other, Consulting fees: Adaptimmune, Alpha Insights, Acuta, Alkermes, Aumbiosciences, Axiom, Baxter, Bayer, Boxer Capital, BridgeBio, COR2ed, COG, Cowen, Ecor1, Gennao Bio, Genentech, Gilead, GLG, Group H, Guidepoint, HCW Precision, ImmunoGen, Infinity, Janssen, Liberium, MedaCorp, Medscape, Numab, Oncologia Brasil, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, RAIN, Seattle Genetics, ST Cube, Takeda, Tavistock, Trieza Therapeutics, Turning Point, WebMD, YingLing Pharma, Ziopharm; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Bayer, Genmab, AACR, ASCO, SITC, Telperian; Financial Interests, Personal, Advisory Role: Molecular Match; Financial Interests, Personal, Other, Founder, Advisor: OncoResponse, Telperian.