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

Cardiff Oncology

Status and phase: Active, not recruiting; Phase 2

Conditions: KRAS/NRAS Mutation; Metastatic Colorectal Cancer; CRC

Treatments: Drug: Bevacizumab; Drug: FOLFOX; Drug: Onvansertib; Drug: FOLFIRI

Study type: Interventional

Funder types: Industry

Identifiers

NCT06106308

CRDF-004

Details and patient eligibility

About

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.

Enrollment: 113 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

113 participants in 6 patient groups

Onvansertib 20mg + Standard of Care

Experimental group

Description:

Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI/BEV on Day 1 and Day 15 of each 28-day treatment cycle.

Treatment:

Drug: FOLFIRI

Drug: Onvansertib

Drug: Bevacizumab

Onvansertib 30 mg + Standard of Care (SOC)

Experimental group

Description:

Participants will receive 30 mg of onvansertib + on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI on Day 1 and Day 15 of each 28-day treatment cycle.

Treatment:

Drug: FOLFIRI

Drug: Onvansertib

Drug: Bevacizumab

Standard of Care (SOC)

Active Comparator group

Description:

Participants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle.

Treatment:

Drug: FOLFIRI

Drug: Bevacizumab

Onvansertib 20 mg + Standard of Care

Experimental group

Description:

Participants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.

Treatment:

Drug: Onvansertib

Drug: FOLFOX

Drug: Bevacizumab

Onvansertib 30 mg + Standard of Care

Experimental group

Description:

Participants will receive 30 mg onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.

Treatment:

Drug: Onvansertib

Drug: FOLFOX

Drug: Bevacizumab

Standard of Care

Active Comparator group

Description:

Participants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle.

Treatment:

Drug: FOLFOX

Drug: Bevacizumab