Testing a Functional Precision Medicine Approach to Select Chemotherapy for Metastatic Colorectal Cancer (COSENSE-1)

Inclusion Criteria: General conditions: 1. Age 18 or older 2. ECOG performance status 0 or 1 3. Obtained informed consent 4. Acceptable organ function (defined in publicly available protocol) 5. Women of child-bearing potential and men must agree to use highly effective contraception (defined in publicly available protocol) Disease and treatment specific conditions: 6. Histologically confirmed pMMR/MSS adenocarcinoma originating from the colon or rectum 7. Unresectable metastatic disease (not amenable to radical surgery of the cancer disease at the time of study inclusion) 8. Patient has metastatic or primary lesion available for biopsy 9. Patient has measurable or evaluable disease per RECIST (version 1.1) 10. The oxaliplatin-based regimen FOLFOX (+/- antibody) versus the irinotecan-based regimen FOLFIRI (+/- antibody), are evaluated by an experienced physician, independent of inclusion in the trial, to be equally recommended for the participant as standard of care first-line therapy in the treatment of mCRC, following the Norwegian national guideline on the treatment of colorectal cancer (https://www.helsedirektoratet.no/retningslinjer/kreft-i-tykktarm-og-endetarm-handlingsprogram) 11. Patient is eligible for full (100%) chemotherapy doses at first treatment cycle 12. Treatment with chemotherapy can be scheduled within 28 days from referral Exclusion Criteria: 1. Patient has metastatic MMR deficient/MSI adenocarcinoma 2. Patient is ineligible for full (100%) chemotherapy doses at first treatment cycle 3. Patient is not equally eligible for FOLFOX (+/- antibody) and FOLFIRI (+/- antibody) chemotherapy regimens, according to the Norwegian national guideline on the treatment of colorectal cancer 4. ECOG performance status 2 or worse 5. Pregnancy or planned pregnancy during the study period, due to the risks of drug treatment to a developing foetus 6. Breastfeeding 7. Patients with psychological, geographical, familial or sociological conditions that can prevent compliance with the study protocol 8. Inability to understand study procedures and comply with them, or disorder that compromises the patient's ability to provide informed consent and/or comply with study procedures 9. Patient fulfils any of the contraindications listed in the SmPC of the relevant IMP 10. Treatment cannot be scheduled within 28 days from referral Medical history: 11. Partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency 12. Evidence of CNS metastasis 13. Unresolved toxicities of a previous systemic treatment that, in the opinion of the physician, make the patient unfit for inclusion 14. Antitumoural treatment ≤ 30 days before inclusion. Hormonal substitutive treatment is allowed 15. Preexisting significant cardiovascular disease including uncontrolled/unstable or symptomatic angina, uncontrolled atrial or ventricular arrythmias, LVEF known to be \< 40% or symptomatic congestive heart failure 16. Stroke (including TIA) or acute myocardial infarction within 6 months before the first dose of study treatment 17. Clinically significant peripheral sensory neuropathy 18. Recent (\<6 months before the start of study treatment) pulmonary embolism, deep vein thrombosis, or another significant thromboembolic event 19. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on chest computed tomography (CT) 20. Evidence of previous acute hypersensitivity reaction to any component of the treatment 21. History of any disease that may increase the risks associated with study participation