OncoMatch/Clinical Trials/NCT06194929
Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma
Is NCT06194929 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including Defactinib and Avutometinib for cutaneous melanoma.
Treatment: Defactinib · Avutometinib · Encorafenib — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Melanoma
Biomarker criteria
Allowed: BRAF mutation
Must have a tumor with a known RAS, BRAF, or NF1 mutation or triple wildtype status using validated testing methods prior to enrollment. Cohorts will be assigned as follows: Cohort A: RAS, BRAF, NF1, or triple wildtype
Allowed: RAS mutation
Must have a tumor with a known RAS, BRAF, or NF1 mutation or triple wildtype status using validated testing methods prior to enrollment. Cohorts will be assigned as follows: Cohort A: RAS, BRAF, NF1, or triple wildtype
Allowed: NF1 mutation
Must have a tumor with a known RAS, BRAF, or NF1 mutation or triple wildtype status using validated testing methods prior to enrollment. Cohorts will be assigned as follows: Cohort A: RAS, BRAF, NF1, or triple wildtype
Allowed: BRAF V600E
Cohort B: BRAF V600E or BRAF V600K
Allowed: BRAF V600K
Cohort B: BRAF V600E or BRAF V600K
Allowed: BRAF triple wildtype
triple wildtype
Disease stage
Metastatic disease required
Performance status
ECOG OR KARNOFSKY 0–1
Prior therapy
Must have received: immunotherapy
Must have received at least 1 line of prior systemic immunotherapy.
Cannot have received: systemic anti-cancer therapy or any investigational therapy
Prior systemic anti-cancer therapy or any investigational therapy ≤ 28 days or within five half-lives prior to starting study treatment, whichever is shorter.
Lab requirements
Blood counts
ANC ≥ 1.5 × 10^9/L; Hemoglobin ≥ 9 g/dL with or without transfusions; Platelets ≥100,000/mm2
Kidney function
Serum creatinine ≤ 1.5 × ULN; OR calculated creatinine clearance > 50 mL/min by Cockcroft-Gault formula; OR estimated glomerular filtration rate > 50 mL/min/1.73m2
Liver function
AST and ALT ≤ 2.5 × ULN; in patients with liver metastases ≤ 5 × ULN; Total bilirubin ≤ 1.5 × ULN; patients with documented Gilbert syndrome or hyperbilirubinemia due to non-hepatic cause may be enrolled
Cardiac function
Adequate cardiac function with left ventricular ejection fraction ≥ 55% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan
Adequate bone marrow, organ function and laboratory parameters: ANC ≥ 1.5 × 10^9/L; Hemoglobin ≥ 9 g/dL with or without transfusions; Platelets ≥100,000/mm2; AST and ALT ≤ 2.5 × ULN; in patients with liver metastases ≤ 5 × ULN; Total bilirubin ≤ 1.5 × ULN; patients with documented Gilbert syndrome or hyperbilirubinemia due to non-hepatic cause may be enrolled; Serum creatinine ≤ 1.5 × ULN; OR calculated creatinine clearance > 50 mL/min by Cockcroft-Gault formula; OR estimated glomerular filtration rate > 50 mL/min/1.73m2; Adequate cardiac function with left ventricular ejection fraction ≥ 55% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- University of Iowa · Iowa City, Iowa
- Huntsman Cancer Institute · Salt Lake City, Utah
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