ASCEND-CRC: Profiling and Targeting Dynamic Tumor Resistance in Patients With Metastatic Colorectal Cancer

Eligibility Criteria * The participant has a histologically or cytologically confirmed diagnosis of colorectal cancer. * Confirmation of non-MSI-H/pMMR status. * Tumor that is measurable as per RECIST v1.1 and biopsy able, defined as lesion/tumor that can be biopsied without undue risk. * Age ≥ 18 years. * ECOG performance status 0-2. * Due to the potential teratogenic effect of chemotherapy, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for an adequate amount of time following end of treatment based on the SOC indications for the administered regimen (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female participants, between the onset of menses and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), In…