92MO - Sotorasib (Soto) + panitumumab (Pmab) and FOLFIRI in previously treated KRASG12C-mutated metastatic colorectal cancer (mCRC): Safety and efficacy for CodeBreaK 101 phase Ib expansion cohort

Background

The combination of Soto and Pmab appears to overcome resistance to KRAS^G12C blockade by mitigating Soto-related upstream EGFR pathway reactivation. In CodeBreaK 101 (NCT04185883) phase 1b study, the combination resulted in 30% ORR in chemorefractory mCRC. We evaluated whether the addition of FOLFIRI to Soto + Pmab would further augment efficacy, with acceptable toxicity, in patients (pts) with KRAS G12C-mutated mCRC who had received ≥1 prior treatment (Tx) for metastatic disease. The fully enrolled dose expansion cohort is reported here.

Methods

KRAS ^G12C inhibitor-naïve pts at 19 global sites were enrolled (Nov 2021‒;Mar 2023) and received the recommended phase 2 dose of Soto (960 mg PO daily) + Pmab (6 mg/kg IV Q2W) and FOLFIRI (IV Q2W). Primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics (PK).

Results

40 pts (47.5% female; median age, 56.0 years) were enrolled (Japan, n=19; Rest of World [ROW], n=21) and treated. Median (range) prior lines of Tx were 2 (1–6). Tx-related adverse events (TRAEs) of any grade occurred in 40 (100%) pts and were consistent with the known AE profiles of the drugs administered. Grade ≥3 TRAEs occurred in 20 (50%) pts, the most common were neutrophil count decrease (22.5%), dermatitis acneiform (10%) and hypomagnesemia (10%). No new safety concerns were identified. Efficacy is shown in the table. Soto PK parameters were similar between Japanese and ROW pts with no clinically meaningful drug interaction. Table: 92MO

Efficacy

*All were partial responses.

Conclusions

These data confirm the promising safety and efficacy for Soto + Pmab and FOLFIRI in previously treated KRAS G12C-mutated mCRC. Data on progression-free survival will be presented.

Clinical trial identification

NCT04185883.

Editorial acknowledgement

Medical writing support was provided by Christopher Nosala (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, Pfizer, Ono, Novartis, Amgen, Syneos Healthe Clinical, Boehringer Ingelheim, Cimic Shift Zero, Eli Lilly. J.H. Strickler: Financial Interests, Personal, Advisory Board: SeaGen, AstraZenca, 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. J. Machiels: Financial Interests, Institutional, Advisory Board: novartis, MSD, Pfizer, Roche, Debio, AstraZeneca, Innate, Nanobiotix, Bayer, Merck-Serono, Boerhinger-Ingelheim, BMS, Pfizer, Cue Pharma, Incyte, Janssen, Johnson & Johnson, ALX Oncology, F-star, nektar, F-star, Seagen, Astellas, genmab; Financial Interests, Institutional, Other, Travel expense: Gilead, MSD, Sanofi; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, MSD; Financial Interests, Institutional, Coordinating PI: MSD, iTeos, eTheRNA; Financial Interests, Institutional, Local PI: Pfizer, Ceylad, MSD, Novartis, KURA, Roche, Lilly, Boehringer, Sanofi-Aventis, Incyte, Bayer, Merck - Serono, Janssen, Johnson & Johnson, Amgen, AbbVie, GSK; Non-Financial Interests, Personal, Leadership Role, Chair: EORTC head and neck group. D.S. Hong: Financial Interests, Personal, Other, Travel, accommodations, expenses: AACR, ASCO, Bayer, Genmab, Gilead, SITC, Telperian; Financial Interests, Personal, Other, Consulting, Speaker, or Advisory Role: Alpha Insights, AbbVie, Adaptimmune, Acuta, Alkermes, Amgen, Bayer, Aumbiosciences, Axiom, Baxter, Boxer Capital, COR2ed, COG, Cowen, Ecor1, Gennao Bio, Genentech, Gilead, GLG, Group H, Guidepoint, HCW Precision, Immunogen, Infinity, Janssen, MedaCorp, Medscape, Numab, Oncologia Brazil, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, RAIN, SeaGen, ST Cube, Turning Point Therapeutics, WebMD, YingLing Pharma, Ziopharm, BridgeBio, Liberium, Takeda, Tavistock, Trieza Therapeutics; Financial Interests, Personal, Advisory Board: 28Bio, Affini-T, Astellas, Fate Therapeutics, CARSgen, InduPro, Projects in Knowledge, Quanta, Ridgeline, Stanford; Financial Interests, Institutional, Research Grant: Adaptimmune, AbbVie, Adlai-Nortye, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Endeavor, Ignyta, Erasca, F. Hoffmann-LaRoche, Fate Therapeutics, Genentech, Genmab, Infinity, Kite, Kyowa Kirin, Loxo, Mologen, Merck, Medimmune, Mirati, Navier, NCI-CTEP, Novartis, Numab, Takeda, Pfizer, Pyramid Bio, SeaGen, VM Oncology, TCR2, Teckro, Turning Point Therapeutics, Biomea, Immunogenesis, Revolution Medicine, STCube; Financial Interests, Personal, Ownership Interest, Advisor: Molecular Match; Financial Interests, Personal, Ownership Interest, Founder, Advisor: OncoResponse, Telperian. R. Greil: Financial Interests, Personal, Advisory Board: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Institutional, Stocks/Shares: Novo Nordisk, Lilly; Financial Interests, Personal and Institutional, Funding: Celgene, Roche, Merck, Takeda, AstraZeneca Novartis, Amgen,BMS, MSD, Sandoz, AbbVie Gilead, Daiichi Sankyo; Non-Financial Interests, Personal, Other, Travel, Accomodation, Expenses, Consulting, Adv Role: Roche, Amgen, Janssen, AstraZeneca Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo, Sanofi; Other, Personal, Other, Travel, Accomodations, Expenses, Consulting, Adv Role., Honoraria: Roche, Amgen, Janssen, AstraZeneca, Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo, Sanofi. E. Chan, J. Hippenmeyer, Y. Saportas, P. Cardona, C. Xia: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. Y. Kuboki: Financial Interests, Personal, Invited Speaker: Taiho, Lilly, Takeda; Financial Interests, Personal, Advisory Role: Incyte, Takeda, Boeringer, Amgen, Abbie; Financial Interests, Personal, Research Grant: Taiho, Astellas, Lilly, Takeda, Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, Incyte, Abbie, Amgen, Merck, Hengrui.