1. Prior exposure to FOLFIRI chemotherapy
2. Clinically significant peripheral neuropathy (>=Grade 3 per CTCAE 5.0)
3. Any untreated central nervous system (CNS) lesion. However, subjects are eligible if: a) all known CNS lesions have been treated with radiotherapy or surgery and b) patient remained without evidence of CNS disease progression ≥4 weeks after treatment.
4. Allogenic bone marrow or solid organ transplant
5. Known history or current interstitial lung disease or non-infectious pneumonitis
6. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion.
7. Known additional malignancy that is progressing or requires active treatment, with the exception of patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or antitumor assessment of the investigational regimen.
8. Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: DPD testing is not mandatory as part of the trial and can be performed at the discretion of treating provider per local requirements)
9. Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment
10. Infection with human immunodeficiency virus (HIV)-1 or HIV-2. (Exception:
Participants with well-controlled HIV [ie, CD4 > 350/mm3 and undetectable viral load] are eligible.)
11. Active hepatitis, including the following:
1. Acute or chronic hepatitis B (Exception: Participants who are hepatitis B surface antigen [HbsAg] positive are eligible if they have hepatitis B virus (HBV) DNA less than 500 IU/mL or 2,500 copies/mL). Note: Participants with detectable HbsAg or detectable HBV DNA should be managed per institutional or local standards. Participants beginning antiviral agents at screening should be treated for > 2 weeks prior to expected date of C1D1.
2. Infection with hepatitis C (Exceptions: [i] Participants who have no history of curative viral treatment and are documented to be viral load negative are eligible; [ii] Participants who have completed curative viral therapy ≥ 12 weeks prior to expected date of C1D1, and viral load is negative are eligible.)
12. Severe chronic or active infections requiring systemic parenteral antibacterial, antifungal or antiviral therapy; or any other potentially life-threatening viral or bacterial infection (participants on oral antibiotics must complete the planned course of treatment prior to expected date of C1D1).
13. Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 14 days or 5 half-lives before enrollment or is currently enrolled in the treatment stage of an investigational study.
14. A woman who is pregnant or breast-feeding, or a woman who is planning to become pregnant or a man who plans to father a child while enrolled in this study or within 150 days after the last dose of study agent.
15. Subject has had a major surgical procedure ≤ 28 days prior to randomization. Subject without complete recovery from a major surgical procedure ≤ 14 days prior to randomization
16. Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
17. Subject has psychiatric illness or social situations such as incarceration that would preclude study compliance, per investigator judgment
18. Patients with a history of perforation, fistula, life-threatening gastrointestinal bleeding, proteinuria (>1 gm/24 hours), wound healing issues
19. Subject has significant cardiovascular disease, including any of the following:
1. Congestive heart failure (defined as New York Heart Association [NYHA] Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident (CVA), or hypertensive crisis within 6 months prior to randomization;
2. History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes);
3. History or family history of congenital long QT syndrome
4. Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible.)
5. Deep venous thrombosis/pulmonary embolism (within last 6 months) unless adequately treated with therapeutic anticoagulation.