NCT06369259

Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To learn if avutometinib in combination with defactinib and cetuximab can help to control unresectable, anti-EGFR-refractory, advanced colorectal cancer.

Detailed description

The primary objective is to assess the antitumor activity of the treatment combinations based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary Objectives: 1. Assess impact of treatment combinations on survival 2. Characterize the safety profile of the treatment combinations (DLTs) 3. Evaluate the pharmacodynamics of the avutometinib combination with defactinib plus cetuximab. 4. Evaluate for pERK and Ki67 inhibition Exploratory Objectives * Assess blood- and tissue-based predictive biomarkers of activity upon treatment with cetuximab plus avutometinib plus defactinib * Demonstrate feasibility of establishing patient-derived xenograft (PDX) models in matched patients with cetuximab-refractory mCRC to evaluate for biomarkers of response and mechanisms of resistance. * Explore mechanisms of resistance to cetuximab plus avutometinib and defactinib

Conditions

• Advanced Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Defactinib	Given by PO
DRUG	Cetuximab	Given by IV
DRUG	Avutometinib	Given by PO

Timeline

• Start date: 2025-02-24
• Primary completion: 2029-02-01
• Completion: 2029-02-01
• First posted: 2024-04-16
• Last updated: 2026-04-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study