Study of Onvansertib in Combination With FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab Versus FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer in Adult Participants With a KRAS or NRAS Mutation

The purpose of this study is to assess 2 different doses of onvansertib to select the lowest dose that is maximally effective, and to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of onvansertib in combination with FOLFIRI + bevacizumab or FOLFOX + bevacizumab in patients with KRAS or NRAS-mutated metastatic colorectal cancer (CRC) in the first-line setting.

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. * 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