91MO - Sotorasib plus panitumumab versus standard-of-care for chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC): CodeBreak 300 phase III study

Background

We report the first phase 3 primary results for sotorasib (soto), a KRAS^G12C-inhibitor, plus panitumumab (pani), an anti-EGFR antibody, vs standard of care (SOC) in patients (pts) with chemorefractory KRAS G12C-mutated mCRC.

Methods

In the CodeBreaK 300 (NCT05198934) global, open label study, 160 pts with chemorefractory KRAS G12C-mutated mCRC were randomized 1:1:1 to soto 960 mg daily plus pani 6 mg/kg IV (soto960+pani; n=53), soto 240 mg daily plus pani 6 mg/kg IV (soto240+pani, n=53), or investigator’s choice of TAS-102 or regorafenib (n=54). Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1. Key secondary endpoints included ORR, DRR, and DCR.

Results

The study met its primary endpoint. Both soto+pani arms demonstrated statistically significant superior PFS compared to SOC: soto960+pani HR=0.49 (95% CI: 0.30, 0.80; p=0.006), and soto240+pani HR=0.58 (95% CI: 0.36, 0.93; p=0.03). Secondary efficacy endpoints are shown in the table. OS was immature at data cutoff. Grade ≥3 TRAEs that occurred in ≥5% pts were dermatitis acneiform (11.3%), hypomagnesaemia (5.7%), and rash (5.7%) for soto960+pani; hypomagnesaemia (7.5%), diarrhoea (5.7%) for soto240+pani; and neutropenia (23.5%), anaemia (5.9%), and hypertension (5.9%) for SOC. There were no fatal TRAEs. Table: 91MO

Efficacy by BICR

CI, confidence interval; DCR, disease control rate; DOR, duration of response; NR = not reached; ORR, objective response rate

Conclusions

In the first phase 3 study for a KRAS^G12C-inhibitor plus an anti-EGFR antibody in chemorefractory mCRC, the primary endpoint was met and both doses of soto+pani showed superior PFS vs SOC. Soto960+pani demonstrated clinically meaningful benefit across PFS and key secondary endpoints (ORR, DCR, DOR) and was tolerable with lower rates of Grade ≥3 TRAEs vs SOC.

Clinical trial identification

NCT05198934.

Editorial acknowledgement

Medical writing support was provided by Christopher Nosala (Amgen Inc.).

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

Y. Kuboki: Financial Interests, Personal, Invited Speaker: Taiho, Lilly, Takeda; Financial Interests, Personal, Advisory Role: Incyte, Takeda, Boeringer, Amgen, Abbie; Financial Interests, Institutional, Research Grant: Taiho, Astellas, Lilly, Takeda, Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, Incyte, Abbie, Amgen, Merck, Hengrui. F. Pietrantonio: Financial Interests, Personal, Advisory Board: Amgen, Merck-Serono, MSD, Bayer, Organon, Astellas; Financial Interests, Personal, Invited Speaker: Amgen, Merck-Serono, BMS, Lilly, Servier, Bayer, Pierre Fabre, AstraZeneca, Astellas; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Incyte, Agenus. L. Salvatore: Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Advisory Role: Pierre Fabre, Merck, Amgen, Servier, Bayer, AstraZeneca, Incyte, GSK, MSD; Financial Interests, Personal, Invited Speaker: Takeda, Pierre Fabre, Merck, Amgen, Servier, Bayer, AstraZeneca, Incyte, GSK, MSD; Financial Interests, Personal, Advisory Board: Pierre Fabre, Merck, Amgen, Servier, Bayer, AstraZeneca, Incyte, GSK, MSD. T. Esaki: Financial Interests, Institutional, Funding: Chugai, Nihon Kayaku; Financial Interests, Institutional, Research Grant: Eisai, Bayer, Asahikasei Pharma, Astellas, Amgen, Biopharma, Parexel, Eli Lilly, Quintiles, Dainippon Sumitomo, Pfizer, Syneos Health Clinical, Daiichi Sankyo, IQVIA, Nihon Kayaku, Chugai, Ono, Novartis, MSD; Financial Interests, Personal, Invited Speaker: Chugai, Taiho, EP force, MSD, Daiichi Sankyo, Eli Lilly, Ono, Bristol. D.P. Modest: Financial Interests, Personal, Invited Speaker: Amgen, Servier, Merck, Onkowissen, MSD, BMS, AstraZeneca, Pierre Fabre, Lilly, Cureteq, GSK, Seagen, Medison, COR2ED, JE, 21up; Financial Interests, Personal, Advisory Board: Amgen, Servier, Merck, MSD, BMS, Incyte, Takeda, G1, Onkowissen, Pierre Fabre, AstraZeneca; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Coordinating PI: Servier. D. Paez: Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Advisory Role: Amgen, Novartis, BMS; Financial Interests, Personal, Invited Speaker: Amgen, Novartis, BMS. J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Astellas, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis; Non-Financial Interests, Personal, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Personal, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, Personal, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships /partnership for FFCD in the prodige intergroup: Federation Francophone de Cancerologie Digestive (FFCD). E. Ruiz: Financial Interests, Personal, Advisory Board: Roche, Amgen, BMS, Bayer, Pfizer; Financial Interests, Personal, Invited Speaker: Roche, Merck, Astellas; Non-Financial Interests, Personal, Member: ASCO. T.W. Kim: Financial Interests, Institutional, Research Grant: Genentech. D. Cunningham: Financial Interests, Personal, Advisory Role: OVIBIO; Financial Interests, Institutional, Research Grant: Medimmune, Clovis, Eli Lilly, 4SC, Bayer, Celgene, Leap, Roche. K. Yeh: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, PhytoHealth, Novartis, Ono, Merck, AstraZeneca; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, American Association for Cancer Research. E. Chan, J. Chao, N. Strydom, Y. Saportas, Q. Tran: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Amgen, Pierre Fabre, Nordic Pharma; 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. Fakih: Financial Interests, Personal, Advisory Board, Consultant: AstraZeneca, Bayer Corporation, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, One meeting: Eisai Oncology; Financial Interests, Personal, Advisory Board, One meeting: Entos, Merck, Seattle Genetics, Xenthera; Financial Interests, Personal, Advisory Board, Also Editorial Boards & Consulting: Mirati Therapeutics; Financial Interests, Personal, Advisory Board: Nouscom, Roche / Genentech; Financial Interests, Personal, Advisory Board, Consulting: Pfizer, Taiho Oncology; Financial Interests, Institutional, Research Grant: AgenusBio, Genentech / imCORE, Verastem. All other authors have declared no conflicts of interest.