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

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.