Clinical trial · Interventional
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
A Phase 2, Randomized, Open-label 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 Patients With a KRAS or NRAS Mutation
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| CRC | Colorectal Carcinoma | ALIAS | 0.90 |
| KRAS/NRAS Mutation | — | UNRESOLVED | — |
| Metastatic Colorectal Cancer | Malignant Colorectal Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Bevacizumab | Drug | Bevacizumab | ALIAS |
| FOLFIRI | Drug | FOLFIRI Regimen | ALIAS |
| FOLFOX | Drug | FOLFOX Regimen | ALIAS |
| Onvansertib | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (6)
- type
- EXPERIMENTAL
- label
- Onvansertib 20mg + Standard of Care
- 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.
- interventionNames
- Drug: Onvansertib
- Drug: FOLFIRI
- Drug: Bevacizumab
- type
- EXPERIMENTAL
- label
- Onvansertib 30 mg + Standard of Care (SOC)
- 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.
- interventionNames
- Drug: Onvansertib
- Drug: FOLFIRI
- Drug: Bevacizumab
- type
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (1)
- DERIVEDAhn DH, Ridinger M, Cannon TL, Mendelsohn L, Starr JS, Hubbard JM, Kasi A, Barzi A, Samuelsz E, Karki A, Subramanian RA, Yemane D, Kim R, Wu CC, Croucher PJP, Smeal T, Kabbinavar FF, Lenz HJ. Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial. J Clin Oncol. 2025 Mar;43(7):840-851. doi: 10.1200/JCO-24-01266. Epub 2024 Oct 30. PMID 39475591