Inclusion Criteria:

- Histologically confirmed metastatic colorectal cancer.

- Documented KRAS or NRAS mutation.

- No previous systemic therapy in the metastatic setting.

- Participants must be willing to submit archival tissue or undergo fresh biopsy for
KRAS/NRAS status.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Women of childbearing potential must use contraception or take measures to avoid
pregnancy.

- Imaging computed tomography (CT) or magnetic resonance imaging (MRI) of
chest/abdomen/pelvis and other scans as necessary to document all sites of disease
performed within 28 days prior to the first dose of onvansertib.

- Must have acceptable organ function

Exclusion Criteria:

- Concomitant KRAS or NRAS and BRAF-V600 mutation or microsatellite instability
high/deficient mismatch repair.

- Prior treatment with a VEGF inhibitor, including bevacizumab or biosimilars.

- Previous oxaliplatin treatment within 12 months prior to randomization, when arm open.

- Known dihydropyrimidine dehydrogenase (DPD) deficiency.

- Anticancer chemotherapy or biologic therapy administered within 28 days prior to the
first dose of study drug.

- Untreated or symptomatic brain metastasis.

- Gastrointestinal (GI) disorder(s) that would significantly impede the absorption of an
oral agent.

- Unable or unwilling to swallow study drug.

- Uncontrolled intercurrent illness.

- Known hypersensitivity to fluoropyrimidine or leucovorin, irinotecan, or oxalipatin.

- Abnormal glucuronidation of bilirubin; known Gilbert's syndrome.

- Use of strong CYP3A4 or CYP2C19 inhibitors or strong CYP3A4 inducers.

- QTc >470

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/5/2024. Questions regarding updates should be directed to the study team contact.