Clinical Research Directory

Inclusion Criteria: * Age ≥ 18 years. * Histologically proven advanced-stage unresectable locally advanced or metastatic colorectal adenocarcinoma. * Proven KRAS G12C mutation as locally assessed by means of an IVDR-compliant test * Agreement to participate to biological studies (blood samples for ctDNA and send tumour block). * Patient with one these criteria: Patient with WHO PS=2 Patient between 70 and 75 years old with WHO PS 1 Patient ≥ 75 years old * Measurable lesion according to the Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1). * No prior treatment for the metastatic disease. Prior adjuvant chemotherapy is allowed if there is more than 6 months between the end of adjuvant treatment and relapse. * Adequate organ function: Hemoglobin \> 9 g/dl, Absolute neutrophil count \> 1500 /mm3, Platelets \> 80 000/mm3, Creatinine clearance rate ≥50 mL/min as calculated using MDRD formula, ALT/AST ≤5×ULN and total bilirubin ≤1.5×ULN. * Ability to understand and sign written informed consent to participate in the study. * Provides written informed consent for the study. * Life expectancy \>6 months. * Women of childbearing potential must agree to use contraception during the trial treatment and for at least 6 months after discontinuation of the experimental treatments. Men who have sexual relationship with women of childbearing potential must agree to use contraception during treatment and for at least 3 months after discontinuation of the experimental treatments. * Patient affiliated to a social security scheme for France, or equivalent for other countries. Exclusion Criteria: \- Patient with one of these criteria: Patient fit for doublet/triplet regimen Patient with WHO PS 3 or 4 Patient \< 75 years old with WHO PS 0 Patient \< 70 years old with WHO PS 0 or 1 * Uncontrolled intercurrent illness including liver (liver cirrhosis Child Pugh B or C) and lung (one second forced expiratory volume \<50%) severe insufficiency. * Patients with high microsatellite instability (MSI-H) or a tumour with mismatched repair (dMMR). * Clinically significant cardiac abnormalities including prior history of any of the following: severe cardiomyopathy, congestive heart failure of New York Heart Association grade ≥3, history of clinically significant (i.e., active) atherosclerotic cardiovascular disease (myocardial infarction, unstable angina, cerebrovascular accident within 6 months prior to the first dose of study treatments). * Patients with Dihydropyrimidine Dehydrogenase (DPD) enzyme deficiencies (uracilemia ≥ 16 ng/mL). * Immunotherapy within 3 months before the beginning of the treatment study. * Patient under treatment by strong CYP3A4 inducers. * Patients treated by brivudine within 4 weeks before the first dose of study treatment, or concomitant treatment with brivudine. * Patient with potentially serious infection. * Administration of live or live attenuated vaccine within 30 days prior to the first dose of study treatment start. * Poor nutritional state (albuminemia \< 25 g/L or weight loss \> 10% during the last month). * Hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption. * Other malignancy within 2 years prior to study enrolment, except for localized cancer in situ, basal or squamous cell skin cancer adequately treated. * Less than 4 weeks from major surgeries and not recovered adequately from the procedure and/or any complications from the surgery. * Patients with persistent toxicities related to prior treatment of grade greater than 1.Is c urrently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 weeks or 5 half-lives (whichever longer) before study entry. * Hypersensitivity to one of the active substances or to one of the excipients of the trial treatments. * Patient with interstitial lung disease or pulmonary fibrosis. * Patients with history of interstitial pneumonitis or pulmonary fibrosis. * Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the study. * Patient who is under judicial protection and patient who is legally institutionalized or under guardianship or not able to give consent. * Pregnant or breastfeeding woman. * Inability to undergo the medical follow-up of the trial for geographical, social or psychological reasons.