NCT06194929

Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma

Phase 1b/2 Trial of Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: University of Utah · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this interventional clinical trial is to provide proof-of-principle data for the biologic activity of defactinib in combination with avutometinib in brain metastases from melanoma, and to define the potential role of the combination with mutant BRAF inhibitors or after BRAF/MEK inhibitors in BRAF V600E/K mutant tumors, in individuals with advanced melanoma who experience the development or progression of brain metastases after treatment with immune checkpoint inhibitors. The main questions it aims to answer are: * What is the preliminary response rate of defactinib and avutometinib in patients with RAS mutant, BRAF mutant, NF1 mutant, triple RAS/BRAF/NF1 wild type (wt) melanoma (including RAF fusions)? * What is the safety and tolerability of the combination of defactinib, avutometinib, and encorafenib in patients with BRAF V600E/K mutant melanoma with at least one untreated brain metastases? * What is the preliminary response rate of the three drug combination of defactinib, avutometinib, and encorafenib in patients with BRAF V600E/K mutant melanoma.

Conditions

• Cutaneous Melanoma
• Brain Metastases

Interventions

Type	Name	Description
DRUG	Defactinib	Defactinib will be administered at 200 mg twice daily orally per arm description.
DRUG	Avutometinib	Avutometinib will be administered at 3.2 mg twice a week orally per arm description.
DRUG	Encorafenib	Encorafinib administered orally per arm description.

Timeline

• Start date: 2024-03-20
• Primary completion: 2028-01-15
• Completion: 2030-01-15
• First posted: 2024-01-08
• Last updated: 2025-12-03

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study