Faculty Collaboration Database

Phase II Study of Dabrafenib and Trametinib in Patients With Tumors With BRAF^V600E Mutations: Updated Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol H. JCO Precis Oncol 2026 Jan;10:e2500338

Date

01/15/2026

Pubmed ID

41533998

Pubmed Central ID

PMC12810769

DOI

10.1200/PO-25-00338

Scopus ID

2-s2.0-105035780149 (requires institutional sign-in at Scopus site)

Abstract

PURPOSE: Subprotocol H of the NCI-MATCH trial demonstrated the efficacy of dabrafenib + trametinib in a cohort of patients with BRAF^V600-mutated treatment-refractory solid tumors and myeloma. To confirm the longer-term efficacy and safety of this combination in additional patients, an expansion cohort was added.

METHODS: Patients with BRAF^V600-mutated malignancies were eligible; patients with cholangiocarcinoma and low-grade serous ovarian cancer were excluded from the expansion cohort. Patients received dabrafenib 150 mg PO twice daily and trametinib 2 mg PO once daily. The primary end point was to evaluate the objective response rate (ORR); secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival (OS).

RESULTS: The expansion cohort enrolled from October 2020 to January 2023. In total, 36 patients were included in the primary efficacy analysis for the combined cohort, including six patients from the expansion cohort and 30 patients from the original cohort, representing 17 different tumor histologies. Fifty-six percent of patients were female, with a median age of 60. The ORR was 36.1% (13 of 36 [90% CI, 22.9 to 51.2]). The median PFS was 11.4 months, and the median OS was 28.6 months. The 6-month PFS was 67.6% (90% CI, 54.5 to 80.8). In the six molecularly confirmed cases in the expansion cohort, there were two responses, including one complete response in a patient with a pilocytic astrocytoma; an additional two patients without molecular confirmation also had PRs. Three patients (two from the original cohort and one from the expansion cohort) remain on therapy. The safety profile was consistent with previous reports with dabrafenib and trametinib.

CONCLUSION: This study confirms the clinical benefit of dabrafenib + trametinib in BRAF^V600-mutated solid tumors, supporting the recent tumor-agnostic regulatory approval of this combination.

Author List

Salama AKS, Wang V, Macrae ER, Park JI, Chen HX, Gray RJ, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Armstrong DK, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT

Author

Jong-In Park PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Female
Humans
Imidazoles
Male
Middle Aged
Mutation
Neoplasms
Oximes
Proto-Oncogene Proteins B-raf
Pyridones
Pyrimidinones