73MO - Sotorasib (soto), panitumumab (pani), and FOLFIRI in first-line (1L) KRAS G12C–mutated metastatic colorectal cancer (mCRC): Regional analysis of safety and efficacy from CodeBreaK 101

Background

Previously in CodeBreaK 101 (NCT04185883), the combination of soto, pani, and FOLFIRI in 1L mCRC demonstrated an acceptable safety profile and a response rate of 75% in patients (pts) with KRAS G12C–mutated mCRC. Here, we evaluated the safety and efficacy of this combination in pts from Japan and rest of the world (ROW).

Methods

Pts with KRAS G12C–mutated mCRC who had not previously received systemic treatment (tx) for metastatic disease were enrolled in 7 countries (Jul 2021–Mar 2024) and received soto (960 mg oral daily), pani (6 mg/kg intravenously [IV] once every 2 weeks [Q2W]), and FOLFIRI (IV Q2W). The primary endpoint was safety. Secondary endpoints included objective response rate (ORR) and disease control rate (DCR).

Results

The fully enrolled cohort, consisting of 40 pts (female, 42.5%; median age, 60 years; Japan, n = 14; ROW, n = 26), received tx. Tx-related adverse events (TRAEs) of any grade occurred in 100% of pts, and grade ≥ 3 TRAEs occurred in 35.7% of Japanese and 65.4% of ROW pts; no fatal events were reported. Thirty pts treated with soto, pani, and FOLFIRI had a confirmed response: 10 pts in Japan and 20 pts in ROW. The combination resulted in an ORR of 71.4% and 76.9% and a DCR of 100% and 92.3% in pts from Japan and ROW, respectively (Table). Table: 73MO

Efficacy

CI, confidence interval; DCR, disease control rate; ORR, objective response rate; ROW, rest of the world.

Conclusions

The combination of soto, pani, and FOLFIRI in the 1L setting had a tolerable safety profile and a promising response rate in pts from Japan and ROW. The phase III CodeBreaK 301 (NCT06252649) study is currently enrolling to evaluate this combination against standard of care in 1L mCRC.

Clinical trial identification

NCT04185883.

Editorial acknowledgement

Medical writing support was provided by Marlesa Godoy, PhD (Amgen Inc.), and Christopher Nosala, PhD, CMPP (Amgen Inc.).

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

T. Masuishi: Financial Interests, Personal, Invited Speaker: Takeda, Chugai, Merck Bio Pharma, Taiho, Bayer, Eli Lilly, Yakult Honsha, Sanofi, Daiichi Sankyo, Ono, Bristol Myers Squibb, MSD, Nippon Kayaku; Financial Interests, Institutional, Funding: Daiichi Sankyo, Ono, Novartis, Amgen, Syneos Healthe Clinical, Boehringer-Ingelheim, Pfizer, Cimic Shift Zero, Eli Lilly, MSD. K. Yamaguchi: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb Japan; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, Bristol Myers Squibb Japan, Chugai Pharma, Daiichi Sankyo, Lilly, Merck, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda; Financial Interests, Institutional, Research Funding: Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharma, Daiichi Sankyo, Eisai, Gilead Sciences, Lilly, MSD Oncology, Ono Pharmaceutical, Sanofi, Taiho Pharmaceutical, Yakult Honsha. J.C. Ruffinelli Rodriguez: Financial Interests, Personal, Invited Speaker: AMGEN; Other, Personal, Other, Travel and accomodation: MSD, Merck, Advanced Accelerator Applications, Esteve. Y. Kuboki: Financial Interests, Personal, Advisory Board: Takeda, Amgen, Abbie, Incyte, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Taiho, Lilly; Financial Interests, Institutional, Local PI: Taiho, Astelas, Lilly, Takeda, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, Incyte, Abbie, Merck, Novartis, Hengrui; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Personal, Member: JSMO, ASCO, JSCO, JCA. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Amgen, Pierre Fabre, Nordic Pharma, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Institutional, Coordinating PI: Roche, Bayer, Servier, Merck; Financial Interests, Institutional, Local PI: seagen, Hutchinson. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Agenus Inc., Amgen, Bayer, Boehringer Ingelheim, Cure Teq AG, Hoffman La - Roche, Janssen, MSD, Merck Serono, Pierre Fabre, RIN Institute Inc., Repare Therapeutics Inc., Sanofi, Servier, Takeda; Financial Interests, Personal, Invited Speaker: BMS, Lilly, Medscape, Novartis, Organon, Pfizer; Financial Interests, Personal, Other, Steering Committee: GSK; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: AbbVie Deutschland Gmbh & Co KG, Amgen Inc., Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bayer Pharma AG, BeiGene, Bioncotech Therapeutics, S.L., BioNTech Rna Pharmacuticals GMBH, BioNTech Small Molecules GMBH, Boehringer Ingelheim, Boehringer Ingelheim de España S.A., Bristol Myers Squibb International Corporation, Celgene International SARL, Daiichi Sankyo, Inc, Debiopharm International SA, Genentech Inc, Gercor, HalioDX SAS, Hoffmann-La Roche Ltd, Hutchinson Medipharma Limited, Hutchison MediPharma International, Iovance Biotherapeutics, Inc., Janssen Research & Development, Janssen-Cilag SA, MedImmune, Menarini, Menarini Ricerche SPA, Merck Health KGAA, Merck Sharp & Dohme de España SA, Merus NV, Mirati, Nouscom SRL., Novartis Farmacéutica SA, Pfizer, PharmaMar SA, Pledpharma AB, Redx Pharma PLC, Sanofi Aventis Recherche & Développement, Scandion Oncology, Seattle Genetics Inc., Servier, Sotio A.S., Taiho Pharma USA Inc, Wntresearch AB; Non-Financial Interests, Personal, Leadership Role, Member of the Scientific Program Committee and Developmental Therapeutics-Immunotherapy Track Leader, 2023-2024 term: American Society for Clinical Oncology (ASCO); Non-Financial Interests, Personal, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Personal, Other, Member of the Scientific Committee 2024: European Society for Medical Oncology (ESMO); Non-Financial Interests, Personal, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Personal, Other, Member of the Scientific Committee SEOM Annual Meeting, 2024-2025 term: Sociedad Española de Oncología Médica (SEOM); Other, Personal, Other, Travel, accommodations, expenses: Agenus Inc., Amgen, BMS, Bayer, Boehringer Ingelheim, Cure Teq AG, GSK, Hoffman La-Roche, Janssen, Lilly, MSD, Medscape, Merck Serono, Novartis, Organon, Pfizer, Pierre Fabre, RIN Institute Inc., Repare Therapeutics Inc., Sanofi, Seagen, Servier, Takeda. J.H. Strickler: Financial Interests, Personal, Stocks or ownership: Triumvira Immunologics; Financial Interests, Personal, Advisory Role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Daiichi, Sankyo/AstraZeneca, GSK, Janssen Oncology, Jazz Pharmaceuticals, Lilly, Merck, Pfizer, Roche/Genentech, Seagen, Taiho Oncology; Financial Interests, Institutional, Advisory Role: Natera; Financial Interests, Institutional, Research Funding: Takeda, A*Star, AbbVie, Amgen, AstraZeneca/MedImmune, Bayer, Beigene, Curegenix, Daiichi Sankyo/Lilly, Erasca, Inc., GSK, Leap Therapeutics, Lilly, Roche/Genentech, Seagen; Financial Interests, Personal, Expert Testimony: Seagen; Financial Interests, Personal, Other, travel, accommodations, expenses: Seagen . M. Furqan: Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca/MedImmune, BeiGene, Jazz Pharmaceuticals, Mirati Therapeutics, Novartis, Omega Therapeutics; Financial Interests, Personal, Speaker’s Bureau: Binaytara Foundation - Education Academy; Financial Interests, Institutional, Research Funding: AbbVie, AbbVie/Stemcentrx, Amgen, AstraZeneca/MedImmune, BeiGene, Biothera, Bristol Myers Squibb/Celgene, Celgene, Checkmate Pharmaceuticals, Elicio Therapeutics, Genentech, Genmab, Gilead Sciences, GSK, Immunocore, Incyte, InhibRx, Jacobus Pharmaceutical Company, Lilly, Merck, Mirati Therapeutics, Novartis, Poseida Therapeutics, SOPHiA Genetics. B. Bashir: Financial Interests, Personal, Advisory Board: Merck/ Eisai, Fate/ Ono Therapeutics, KAHR Medical; Financial Interests, Personal, Other, Scientific reviewer: Department of Defense, United States; Financial Interests, Institutional, Local PI: Amgen Inc., Avenzo Therapeutics, Bicycle Therapeutics, Boehringer Ingelheim, Elucida Oncology, Gritstone Bio, Jazz Pharmaceuticals, KAHR Medical, Lyell Immunopharma, Merck, Ikena Oncology, Pionyr Immunopharma, RASCAL Therapeutics, Syros Pharmaceuticals, Tarveda Therapeutics; Financial Interests, Personal and Institutional, Steering Committee Member: Fate Therapeutics. C. Nduka, J. Hippenmeyer, E. Chan, C. Xia: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. S. Siena: Financial Interests, Personal, Advisory Board, Advisory Board Member: Agenus, AstraZeneca, BMS, Checkmab, Daiichi Sankyo, GSK, Novartis, Seagen, T-One-Therapeutics, Merck, MSD. All other authors have declared no conflicts of interest.