Abstract 59P
Background
CodeBreaK 300 (CB300) (NCT05198934) and CodeBreaK 101 (CB101) (NCT04185883) evaluated soto960 plus pani in patients (pts) with chemorefractory KRAS G12C-mutated mCRC. In CB300, soto960 plus pani improved progression-free survival (PFS) vs physician’s choice. In the phase 3 SUNLIGHT (SL) study (NCT04737187), treatment (tx) with T/T plus bev resulted in longer survival vs T/T in pts with unselected refractory mCRC. MAICs were preformed to compare the efficacy and safety of soto960 plus pani vs T/T plus bev.
Methods
Clinical outcomes and adverse events (AEs) were compared in pts who received soto960 plus pani in CB300 and CB101 (pooled n = 93) and T/T plus bev in SL (n = 246). By matching pt selection criteria across trials and weighting individual pt-level data from the pooled CB studies, differences in available baseline characteristics considered to be prognostic factors were adjusted with the MAIC. Odds ratios (OR) were estimated for objective response rates, hazard ratios (HR) were used for PFS and overall survival (OS). AEs were compared descriptively.
Results
The effective sample size of soto960 plus pani with matched characteristics consisted of 31 pts. MAIC results showed tx with soto960 plus pani increases the likelihood of response to tx, with an adjusted OR of 6.0 vs T/T plus bev (Table). The HR for PFS was 0.85 demonstrating a numerical trend favoring soto960 plus pani. Grade 3+ tx-emergent AEs occurred in 51% and 72% of soto960 plus pani and T/T plus bev-treated pts, respectively. Comparison of OS will be presented based on pooled data from CB101 and CB300.
Conclusions
Soto960 plus pani is associated with a statistically significant and clinically meaningful improvement in response rates and a numerical improvement in PFS vs T/T plus bev. The analyses are limited by decreased sample size for soto960 plus pani and lack of KRAS G12C-specific data in the SL study. Table: 59P
| Soto960 plus pani | T/T plus bev | |
| Objective response rate ∗ | 27.9% | 6.1% |
| OR (95% CI) | 6.0 (2.7-13.2) | |
| Median PFS, months | 6.3 | 5.6 |
| HR PFS (95% CI) | 0.85 (0.52-1.38) |
∗Per central review for soto960 plus pani, per investigator for T/T plus bev.
Editorial acknowledgement
Medical writing support was provided by Marlesa Godoy, PhD (Amgen Inc.).
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
L. Salvatore: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bayer, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Servier; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Servier; Financial Interests, Personal, Invited Speaker, Travel, Accommodation, Expenses: Bayer, Celgene, Merck Serono, Pierre Fabre, Sanofi, Servier. 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. Y. Kuboki: Financial Interests, Personal, Advisory Board: Takeda, Amgen, Abbie, Incyte, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Taiho, Lilly; Financial Interests, Institutional, Invited Speaker: Taiho, Astellas, Lilly, Takeda, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, Incyte, Abbie, Amgen, Merck, Novartis, Hengrui; Non-Financial Interests, Member: JSMO, ASCO, JSCO, JCA. D.S. Hong: Financial Interests, Personal, Other, Travel, accommodation, 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, Advisory Board: 28Bio, Affini-T, Astellas, Fate Therapeutics, CARSgen, InduPro, Projects in Knowledge, Quanta, Ridgeline, Stanford; 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, Biomea, Immunogenesis, Revolution Medicine, STCube. D.P. Modest: Financial Interests, Personal, Invited Speaker: Takeda, Taiho, Amgen, Servier, Merck, Onkowissen, MSD, AstraZeneca, Pierre Fabre, GSK, Medison, COR2ED, JE, 21up, Seagen; Financial Interests, Personal, Advisory Board: Amgen, Servier, Merck, MSD, Takeda, G1, Onkowissen, Pierre Fabre, AstraZeneca, Regeneron; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Invited Speaker: Servier. J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis, Pfizer, Sanofi, Rottapharm, Takeda; Financial Interests, Personal, Expert Testimony: Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis; Financial Interests, Personal, Invited Speaker, symposia: Astellas; Financial Interests, Personal, Other, steering committee of clinical trial: Novartis; Non-Financial Interests, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, 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); Non-Financial Interests, Other, steering committee of clinical trials: Pfizer, Servier. T.J. Price: Financial Interests, Personal, Advisory Board, Global advisory board on MSS CRC: MSD; Financial Interests, Personal, Invited Speaker: Amgen; Non-Financial Interests, Advisory Role, Advisory board uncompensated: MSD; Non-Financial Interests, Advisory Role: Takeda, Servier. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Pierre Fabre, Nordic Pharma, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Institutional, Invited Speaker: Roche, Bayer, Servier, Merck, Seagen, Hutchinson. I.M. Majer: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Amgen. M. Rehn, E. Chan, Z. Chen, Q. Tran: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. F. Pietrantonio: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, MSD, Bayer, Astellas, Takeda, GSK, Johnson&Johnson, Rottapharm; Financial Interests, Personal, Invited Speaker: Amgen, Merck Serono, BMS, Lilly, Servier, Bayer, Pierre Fabre, AstraZeneca, Astellas, Daiichi Sankyo, Takeda; Financial Interests, Personal, Expert Testimony: Ipsen; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Incyte, Agenus; Financial Interests, Institutional, Invited Speaker: Lilly, Amgen.