NCT06106308

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

Active, enrolled Phase 2 Last updated 9 January 2026

What this trial tests

Phase 2 trial testing Onvansertib in Metastatic Colorectal Cancer in 113 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

27 February 2024

Primary endpoint
1 November 2026

1 January 2027

Quick facts

Lead sponsor	Cardiff Oncology
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	113
Start date	27 February 2024
Primary completion	1 November 2026
Estimated completion	1 January 2027
Sites	41 locations across United States

Drugs / interventions tested

• Onvansertib (onvansertib) — full drug profile →
• FOLFIRI (folfiri) — full drug profile →
• Bevacizumab (Bevacizumab-Bvzr) — full drug profile →
• FOLFOX (folfox) — full drug profile →

Conditions studied

• Metastatic Colorectal Cancer — all drugs for Metastatic Colorectal Cancer →
• CRC — all drugs for CRC →
• KRAS/NRAS Mutation — all drugs for KRAS/NRAS Mutation →

Sponsor

Cardiff Oncology — full company profile →

Who can join

18 and older, any sex, with Metastatic Colorectal Cancer or CRC. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Objective Response Rate (ORR)
  Time frame: Up to approximately 1 year
  ORR defined as the proportion of participants who achieved a best overall Response (BOR) of CR or PR per RECIST Version 1.1 from randomization until disease progression, or death due to any cause, as determined by blinded independent central review.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of <i>KRAS</i>-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial.
   Ahn DH, Ridinger M, Cannon TL, Mendelsohn L, et al · · 2025 · cited 18× · PMID 39475591 · DOI 10.1200/jco-24-01266
2. Exploring Predictive and Prognostic Biomarkers in Colorectal Cancer: A Comprehensive Review.
   Ashouri K, Wong A, Mittal P, Torres-Gonzalez L, et al · · 2024 · cited 14× · PMID 39199569 · DOI 10.3390/cancers16162796
3. Current and emerging concepts for systemic treatment of metastatic colorectal cancer.
   Steup C, Kennel KB, Neurath MF, Fichtner-Feigl S, et al · · 2025 · cited 10× · PMID 41047178 · DOI 10.1136/gutjnl-2025-335412
4. PLK1 Inhibitor Onvansertib Enhances the Efficacy of Alpelisib in <i>PIK3CA</i>-Mutated HR-Positive Breast Cancer Resistant to Palbociclib and Endocrine Therapy: Preclinical Insights.
   Sreekumar S, Montaudon E, Klein D, Gonzalez ME, et al · · 2024 · cited 6× · PMID 39409880 · DOI 10.3390/cancers16193259
5. MYC at the tumor-immune interface: mechanisms of immune escape and immunotherapy resistance.
   González-Larreategui Í, Valdés-Bango Martín M, Casacuberta-Serra S, Soucek L. · · 2026 · PMID 41659859 · DOI 10.3389/fimmu.2026.1738440
6. Clinical management and therapeutic development for the rare disease rhabdomyosarcoma.
   Ke TL, Chen L. · · 2026 · PMID 41584037 · DOI 10.7150/jca.127496
7. Clinical relevance of PLK1 in epithelial ovarian cancer.
   Shen X, Wang J, Chen S, Zhang H, et al · · 2025 · PMID 41458961 · DOI 10.3389/fphar.2025.1702273