Phase II Study of Dabrafenib and Trametinib in Patients with Tumors with BRAFV600E Mutations: Updated Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol H
Abstract
Purpose: Subprotocol H of the NCI-MATCH trial demonstrated the efficacy of dabrafenib + trametinib in a cohort of patients with BRAFV600 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 BRAFV600 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 BID and trametinib 2 mg PO daily. The primary endpoint was to evaluate the objective response rate (ORR); secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Results: The expansion cohort enrolled from October 2020-January 2023. In total, 36 patients were included in the primary efficacy analysis for the combined cohort, including 6 patients from the expansion cohort and 30 patients from the original cohort, representing 17 different tumor histologies. 56% of patients were female, with a median age of 60. The ORR was 36.1% (13/36; 90% CI 22.9–51.2%). Median PFS was 11.4 months, and median OS was 28.6 months. 6-month PFS was 67.6% (90% CI 54.5–80.8%). In the 6 molecularly confirmed cases in the expansion cohort, there were 2 responses, including 1 complete response in a patient with a pilocytic astrocytoma; an additional 2 patients without molecular confirmation also had PRs. 3 patients (2 from the…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 36 participants or records.
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