505O - Sotorasib (soto), panitumumab (pani) and FOLFIRI in the first-line (1L) setting for KRAS G12C–mutated metastatic colorectal cancer (mCRC): Safety and efficacy analysis from the phase Ib CodeBreaK 101 study

Background

In the phase 1b CodeBreaK 101 (NCT04185883) study, the addition of soto plus pani to FOLFIRI demonstrated an acceptable safety profile and a promising response rate of 60% for patients (pts) with previously treated KRAS G12C–mutated mCRC. Here, we evaluate the safety and efficacy of soto, pani, and FOLFIRI in treatment (Tx)-naïve pts with KRAS G12C–mutated mCRC.

Methods

Pts with KRAS G12C–mutated mCRC who had not received any prior systemic Tx for metastatic disease were enrolled at 17 global sites (between Jul 2021 and Mar 2024) and received the recommended phase 2 dose of soto (960 mg, oral, daily), pani (6 mg/kg, intravenous [IV], once every 2 weeks [Q2W]), and FOLFIRI (IV Q2W). Primary endpoint was safety and tolerability. Secondary endpoints included objective response rate, disease control rate, and median time to response.

Results

Forty pts were enrolled and treated (58% male; median age: 60 years). Tx-related adverse events (TRAEs) of any grade occurred in 100% of pts, and grade ≥ 3 TRAEs occurred in 53% of pts; no fatal event was reported. The most common grade ≥ 3 TRAEs included neutropenia (23%), dermatitis acneiform (18%), and diarrhea (10%). 30 pts had confirmed partial responses, with an overall response rate of 75%. Treatment with soto, pani, and FOLFIRI resulted in a disease control rate of 93% and median time to response of 1.5 months. Table: 505O

^∗Data are presented as n (%) unless indicated otherwise.

Conclusions

This study provides the first data set on the use of a KRAS^G12C inhibitor in 1L mCRC. The combination of soto, pani, and FOLFIRI demonstrated a tolerable safety profile and promising response rates in pts with Tx-naïve KRAS G12C–mutated mCRC. CodeBreaK 301 (NCT06252649), a phase 3 study, is currently enrolling to evaluate this combination in 1L mCRC against standard of care.

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

S. Siena: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Bayer, Bristol Myers Squibb, CheckmAb, Daiichi-Sankyo, GSK, MSD, Merck, Norvartis, Pierre-Fabre, Seagen, T-One Therapeutics. K. Yamaguchi: Financial Interests, Personal, Invited Speaker: Taiho Pharm; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Bristol Myers Squibb, Ono Pharm, Eli Lilly Japan; Financial Interests, Institutional, Funding: Taiho Pharm. J.C. Ruffinelli Rodriguez: Financial Interests, Personal, Invited Speaker: Amgen; Other, Travel, Accommodations, Expenses: MSD, Merck, Advanced Accelerator Applications. Y. Kuboki: Financial Interests, Personal, Advisory Board: Takeda, Amgen, AbbVie, Incyte, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Taiho, Lilly; Financial Interests, Institutional, Local PI: Taiho, Astellas, Lilly, Takeda, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, Incyte, AbbVie, Merck, Novartis, Hengrui; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, 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: Hoffman La - Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD, Takeda, Boehringer Ingelheim, Cure Teq AG, Repare Therapeutics Inc., RIN Institute Inc., Janssen; Financial Interests, Personal, Invited Speaker: Organon, Novartis, Pfizer, BMS, Lilly, Medscape; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd, Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGAA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune, Abbvie Deutschland Gmbh & Co KG, Bayer Pharma AG, Bioncotech Therapeutics, S.L., Biontech Rna Pharmacuticals GMBH, Biontech Small Molecules GMBH, Boehringer Ingelheim de España S.A., Daiichi Sankyo, Inc, Gercor, Hutchinson Medipharma Limited, Iovance Biotherapeutics, Inc., Janssen Research & Development, Menarini Ricerche SPA, Merck, Sharp & Dohme De España S.A., Nouscom SRL., Pledpharma AB, Redx Pharma PLC, Scandion Oncology, Seattle Genetics Inc., Sotio A.S., Wntresearch AB; Non-Financial Interests, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Non-Financial Interests, 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, Other, Member of the Scientific Committee 2024: European Society for Medical Oncology (ESMO); Other, Travel, Accommodations, Expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. J.H. Strickler: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca, Amgen, Pfizer, Bayer, Abbvie, Natera, Viatris, BeiGene, Silverback Therapeutics, Daiichi-Sankyo, Eli Lilly, Roche Genentech, Takeda, Zentalis, Taiho; Financial Interests, Personal, Other, Consulting: GSK, Pionyr Immunotherapeutics; Financial Interests, Institutional, Coordinating PI: Seagen, Amgen; Financial Interests, Institutional, Local PI: Roche Genentech, Abbvie, AstraZeneca, AStar D3, Bayer, Curegenix, Nektar, Leap Therapeutics, Daiichi Sankyo, Erasca, BeiGene, Silverback Therapeutics. M. Furqan: Financial Interests, Personal, Advisory Board: Abbvie, AstraZeneca/MedImmune, BeiGene, Jazz Pharmaceuticals, Mirati Therapeutics, Novartis, Omega Therapeutics ; Financial Interests, Institutional, Funding: Abbvie, Abbvie/Stemcentrx, Amgen, AstraZeneca/MedImmune, BeiGene, Biothera, Bristol Myers Squibb/Celgene, Celgene, Checkmate Pharmaceuticals, Elicio Therapeutics, Genentech, Genmab, Gilead Sciences, GSK, Incyte, Jacobus Pharmaceutical Company, Lilly, Merck, Mirati Therapeutics, Novartis. B. Bashir: Financial Interests, Personal and Institutional, Research Grant: Defense Congressionally Directed Medical Research Program; Financial Interests, Personal, Speaker, Consultant, Advisor: Fate/Ono Therapeutics, Merck/Eisai, KAHR Medical; Financial Interests, Institutional, Funding: Amgen, Boehringer Ingelheim, Bicycle Therapeutics, Elucida Oncology, Gritstone Bio, Ikena Oncology, Jazz Pharmaceuticals, Kahr Medical, Lyell Immunopharma, Merck, Pionyr Immunopharma, Rascal, Syros, Tarveda. C. Nduka: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. J. Hippenmeyer: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. E. Chan: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. C. Xia: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. 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. All other authors have declared no conflicts of interest.