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 Mu

• Status: Recruiting
• Trial end date: 2027-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cardiff Oncology
• Collaborator: Pfizer
• Treatments: Bevacizumab; Onvansertib

Criteria

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