45MO - Sotorasib in combination with panitumumab in refractory KRAS G12C-mutated colorectal cancer: Safety and efficacy for phase Ib full expansion cohort

Background

Sotorasib (Soto), a KRAS^G12C inhibitor, showed modest clinical activity as monotherapy in heavily pretreated patients (pts) with KRAS G12C-mutated colorectal cancer (CRC) in the CodeBreaK 100 phase 2 study, with a 9.7% objective response rate (ORR). Early data from the CodeBreaK 101 phase 1b dose exploration (n=8) and expansion (n=18) cohorts showed promising antitumor activity for the combination of Soto and panitumumab (Pmab), an EGFR antibody, in chemorefractory KRAS G12C-mutated metastatic CRC (mCRC). Here, we report results from the fully enrolled dose expansion cohort of 40 pts with refractory mCRC.

Methods

CodeBreaK 101 (NCT04185883) subprotocol H includes dose exploration and expansion in multiple cohorts. Key eligibility criteria for the refractory mCRC cohort included progression on or after prior fluoropyrimidine, oxaliplatin, irinotecan and an anti-angiogenic agent. Primary endpoint is safety. Secondary endpoints include antitumor activity, progression-free survival (PFS), overall survival (OS), and pharmacokinetics (PK).

Results

As of March 25, 2022, 40 pts (75% female, median age 57.5 years) were enrolled and received oral Soto 960 mg daily and Pmab 6 mg/kg IV every 2 weeks. Median prior lines of therapy was 2. Treatment-related adverse events (TRAEs) of any grade occurred in 37 (92.5%) pts. Grade 3 TRAEs occurred in 9 (22.5%) pts; related to Soto and Pmab in 6 (15%) and 8 (20%) pts, respectively. No TRAEs were Grade >3 or resulted in treatment discontinuation. Safety findings were consistent with known profiles of Soto and Pmab. Confirmed ORR was 30% (95% CI: 16.6, 46.5). Disease control rate was 90% (95% CI: 76.3, 97.2). Tumor shrinkage of any magnitude was observed in 35 (87.5%) pts. Soto PK exposures were consistent to those observed in monotherapy studies.

Conclusions

This dataset provides further evidence of safety and tolerability for the combination of Soto and Pmab in heavily pretreated pts with KRAS G12C-mutated mCRC, with 3-fold higher response than previously observed with Soto monotherapy, supporting further development of this combination. Longer follow up data with duration of response, PFS, and OS will be presented.

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

Y. Kuboki: Financial Interests, Institutional, Research Grant: Amgen, Taiho, Astelas, Lilly, Takeda, Daiichi-Sankyo, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, GlaxoSmithKline, Incyte, Abbie; Financial Interests, Personal, Advisory Role, Consulting fees: Taiho, Takeda, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Speaker’s Bureau: Taiho, Ono, Lilly, Bristol Myers Squibb. R. Yaeger: Financial Interests, Personal, Advisory Board: Pfizer, Natera, Mirati Therapeutics; Financial Interests, Institutional, Invited Speaker: Mirati Therapeutics, Boehringer Ingelheim, Pfizer. M. Fakih: Financial Interests, Institutional, Research Grant: Genentech, Verastem; Financial Interests, Personal, Advisory Role, Consulting fees: AstraZeneca, Bayer Corporation, HalioDX, Incyte Corporation, Mirati, Pfizer, Inc, PsiOxus, Taiho Oncology, Zhuhai Yufan Biotech; Financial Interests, Personal, Speaker’s Bureau: Amgen Inc; Financial Interests, Personal, Invited Speaker: Guardant360; Financial Interests, Personal, Advisory Board: Amgen Inc, Bayer Corporation, GlaxoSmith Kline, Nouscom, Roche/Genentech, Seattle Genetics; Financial Interests, Institutional, Product Samples: 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. 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; Financial Interests, Institutional, Funding: Daiichi Sankyo, Ono, Novartis, Amgen, Syneos Healthe Clinical, Boehringer-Ingelheim, Pfizer, Cimic Shift Zero, Eli Lilly. 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, Advisory Role: Eisai, Taiho, Celgene, Lilly; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Advisory Board: Lilly. C.M. Bestvina: Financial Interests, Institutional, Research Grant: AstraZeneca, BMS; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, CVS, Genentech, Jazz, JNJ, Novartis, Pfizer, Regeneron/Sanofi, Seattle Genetics, Takeda; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Other, Travel reimbursement: EMD Serono. C.J. Langer: Financial Interests, Personal, Advisory Role, Honoraria, consulting/advisory role: Bristol Myers Squibb, Genentech/Roche, Lilly/ImClone, AstraZeneca, Merck; Financial Interests, Personal, Advisory Role, Honoraria: Takeda Science Foundation; Financial Interests, Personal, Advisory Role, Consulting/advisory role: Abbott Biotherapeutics, Bayer/Onyx, Clarient, Clovis Oncology, Celgene, Cancer Support Community, ARIAD, Takeda, Pfizer, Novocure, Gilead Sciences; Financial Interests, Institutional, Research Grant: Merck, Advantagene, Clovis Oncology, Celgene, Inovio Pharmaceuticals, Ariad, GlaxoSmithKline, Genentech/Roche, Stem CentRx, Lilly, Trizell. J.C. Krauss: Financial Interests, Institutional, Invited Speaker, Site PI for clinical trial: Sumitomo Dainippon Pharma Oncology, Inc., Novartis Pharmaceuticals Corporation, Amgen, Inc., Merck Sharp & Dohme Res. Labs TO Nsabp Foundation; Financial Interests, Institutional, Invited Speaker, Site PI for clinical Trial: Hutchison Medipharma Limited TO Syneos Health, LLC, Ignyta, Inc. TO Quintiles, Inc; Financial Interests, Institutional, Invited Speaker, Site PI for Clinical Trial: Isofol Medical AB; Financial Interests, Institutional, Invited Speaker, Site PI for a clinical trial: AbbVie, Inc., Bristol Myers Squibb, MedImmune, Pfizer, Daiichi Sankyo Company, Ltd. TO Syneos Health, LLC. S. Puri: Financial Interests, Personal, Advisory Role, Consulting fees: AstraZeneca, G1 Therapeutics. P. Cardona, E.K. Chang, Q. Tran: Financial Interests, Personal, Full or part-time Employment: Amgen Inc; Financial Interests, Personal, Stocks/Shares: Amgen Inc. 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: AbbVie, Adaptimmune, Alpha Insights, Acuta, Alkermes, Amgen, 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, SeaGen, ST Cube, Takeda, Tavistock, Trieza Therapeutics, Turning Point Therapeutics, WebMD, YingLing Pharma, Ziopharm; Financial Interests, Personal, Ownership Interest, Advisor: Molecular Match; Financial Interests, Personal, Ownership Interest, Founder, Advisor: OncoResponse, Telperian; Financial Interests, Institutional, Research Grant: AbbVie, Adaptimmune, Adlai-Nortye, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Deciphera, Eisai, Eli Lilly, Endeavor, Erasca, F. Hoffmann-LaRoche, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa Kirin, Loxo, Merck, Medimmune, Mirati, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, SeaGen, Takeda, TCR2, Teckro, Turning Point Therapeutics, VM Oncology.