Eligibility

Inclusion Criteria:

• Age ≥18 years
• Histological or cytological documentation of adenocarcinoma of the colon or rectum that is metastatic (all other histological types are excluded)
• Subjects who progressed or demonstrated intolerability to prior standard approved therapies which include fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapies, cetuximab/panitumumab (if clinically indicated e.g., RAS wild-type tumors) PD-1 or BRAF inhibitors (if clinically indicated), and/or other checkpoint inhibitors in the metastatic setting.
• Previous treatment with any investigational drug or anticancer treatment must be completed >28 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
• Adequate bone marrow, liver, and renal function

Exclusion Criteria:

• Untreated brain metastases, spinal cord compression, or primary brain tumor
• Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
• Evidence of uncontrolled or unstable cardiovascular disease, myocardial infarction (within 6 months), unstable angina pectoris, congestive heart failure, serious arrhythmias requiring drug therapy
• History of CNS disease
• Bevacizumab or aflibercept therapy ≤ 3 weeks prior to starting study treatment
• Peripheral neuropathy Grade ≥ 2
• Uncontrolled hypertension or diabetes mellitus, active peptic ulcers, unhealed wounds, clinically significant disease or systemic infections
• Known seropositive for, or active infection with hepatitis B or C virus
• Symptomatic or uncontrolled infection with human T-cell leukemia virus
• Venous thromboembolism (unless appropriately treated and stable on anticoagulant for at least 2 weeks).