Abstract 1416TiP
Background
Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation is an oncogenic driver mutation that occurs in approximately 13% of NSCLC and is often associated with poor prognosis. Sotorasib is a first-in-class small molecule that specifically and irreversibly inhibits KRASG12C by locking it in its inactive GDP-bound state. Results from the first-in-human trial of sotorasib (CodeBreak 100, NCT03600883) demonstrated a favorable safety profile and promising and durable antitumor activity in patients with KRAS p.G12C mutant advanced NSCLC. These findings supported the initiation of a phase 3 trial of sotorasib versus docetaxel.
Trial design
CodeBreak 200 is a global, randomized, open label, study of sotorasib versus docetaxel in NSCLC pts with KRAS p.G12C mutation. Key eligibility criteria include age of ≥ 18 years, locally-advanced and unresectable or metastatic NSCLC, KRAS p.G12C mutation confirmed by central molecular testing, progression on at least 1 prior systemic therapy, past treatment with platinum-based doublet chemotherapy and checkpoint inhibitor given either as one line of therapy or as individual lines, and performance status ECOG 0/1. Patients with active brain metastases or significant cardiovascular disease will be excluded. Sotorasib or docetaxel will be administered for 21-day cycles until progression, start of another anticancer therapy, unacceptable toxicity, withdrawal of consent, lost to follow up, or death, whichever occurs earliest. The primary endpoint is progression-free survival, as assessed by blinded independent central review per RECIST v1.1. Key secondary endpoints include overall survival, objective response rate as assessed per RECIST v1.1, and patient-reported outcomes as assessed by EORTC QLQ-LC13 and QLQ-C30. Approximately 650 pts will be enrolled in the study globally.
Clinical trial identification
NCT04303780.
Editorial acknowledgement
Medical writing support was provided by Liz Leight (Amgen Inc.).
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
M. Reck: Honoraria (self), Honoraria for lectures and consultancy : AbbVie; Honoraria (self), Honoraria for lectures and consultancy : Amgen; Honoraria (self), Honoraria for lectures and consultancy : AstraZeneca; Honoraria (self), Honoraria for lectures and consultancy : BMS; Honoraria (self), Honoraria for lectures and consultancy : Boehringer Ingelheim; Honoraria (self), Honoraria for lectures and consultancy: Lilly; Honoraria (self), Honoraria for lectures and consultancy : Merck; Honoraria (self), Honoraria for lectures and consultancy : MSD; Honoraria (self), Honoraria for lectures and consultancy : Novartis; Honoraria (self), Honoraria for lectures and consultancy : Pfizer; Honoraria (self), Honoraria for lectures and consultancy : Roche; Honoraria (self), Honoraria for lectures and consultancy : Samsung. A. Spira: Advisory/Consultancy, Research grant/Funding (institution): Amgen. B. Besse: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BeiGene; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Onxeo; Research grant/Funding (institution): OSE Immunotherapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Tiziana Pharma; Research grant/Funding (institution): Tolero Pharmaceuticals. J. Wolf: Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Blueprint; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai; Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ignyta; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Loxo; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda. F. Skoulidis: Travel/Accommodation/Expenses: Tango Therapeutics; Honoraria (institution), Honoraria for educational activity within MD Anderson: BMS. H. Borghaei: Research grant/Funding (institution): Millennium; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: EMD-Serono; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: Genmab; Advisory/Consultancy: Regeneron; Advisory/Consultancy: BioNTech; Advisory/Consultancy: Cantargia AB; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Axiom; Advisory/Consultancy: PharmaMar; Advisory/Consultancy, Leadership role, Data and Safety Monitoring Board: Takeda; Advisory/Consultancy: Huya Bio; Advisory/Consultancy: GLG; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Leadership role, Data and Safety Monitoring Board: University of Pennsylvania; Leadership role, Data and Safety Monitoring Board: Incyte; Shareholder/Stockholder/Stock options, Officer/Board of Directors, Scientific Advisory Board: Sonnetbio; Shareholder/Stockholder/Stock options, Officer/Board of Directors, Scientific Advisory Board: Rgenix; Honoraria (self): Pfizer. K. Goto: Honoraria (self), Research grant/Funding (institution): Astellas Pharma Inc.; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self): Guardant Health Inc.; Honoraria (self): IQVIA Services Japan K.K.; Honoraria (self), Research grant/Funding (institution): Janssen Pharmaceutical K.K.; Honoraria (self), Research grant/Funding (institution): Kyowa Hakko Kirin Co., Ltd; Honoraria (self), Research grant/Funding (institution): Life Technologies; Honoraria (self), Research grant/Funding (institution): Lilly; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): Nippon Kayaku; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Otsuka Pharmaceutica; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Takeda; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Loxo; Research grant/Funding (institution): Medical & Biological Laboratories Co., Ltd; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Riken Genesis; Research grant/Funding (institution): Sumitomo Dainippon; Research grant/Funding (institution): Sysmex Corporation; Research grant/Funding (institution): Xcoo. K. Park: Advisory/Consultancy: Amgen. F. Griesinger: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Blueprint; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Siemens; Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie. E. Felip: Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Blueprint; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony: GSK; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Guardant Health; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Medscape; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck KGaA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: priME Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Samsung; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: Touchime; Officer/Board of Directors, board, independent member: Grifols; Research grant/Funding (institution): Fundación Merck Salud; Research grant/Funding (institution): Grant for Oncology Innovation EMD Serono. M. Boyer: Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Advisory Board member: Merck Sharpe & Dohme; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Advisory Board member: AstraZeneca; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Advisory Board member: Roche; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Advisory Board member: Bristol-Myers Squibb; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Ascentage Pharma. C.H. Barrios: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp Dohme; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): PharmaMar; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: GSK; Advisory/Consultancy: Eisai; Advisory/Consultancy: Bayer. G. Goss: Advisory/Consultancy, Travel/Accommodation/Expenses, Advisory Board member: AstraZeneca; Advisory/Consultancy, Advisory Board member: Pfizer; Advisory/Consultancy, Advisory Board member: Bristol-Myers Squibb; Advisory/Consultancy, Advisory Board member: Celgene. H. Yang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Amgen. C. Obiozor: Shareholder/Stockholder/Stock options, Full/Part-time employment: Amgen. S.S. Ramalingam: Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Scientific Advisory Board member: Amgen; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Scientific Advisory Board member: AstraZeneca; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Scientific Advisory Board member: Bristol-Myers Squibb; Advisory/Consultancy, Leadership role, Scientific Advisory Board member: Roche; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Scientific Advisory Board member: Merck; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Scientific Advisory Board member: Takeda; Advisory/Consultancy, Leadership role, Scientific Advisory Board member: Daiichi Sankyo; Advisory/Consultancy, Leadership role, Scientific Advisory Board member: GSK; Research grant/Funding (institution): Genmab; Research grant/Funding (institution): Tesaro.