Dabrafenib and trametinib in patients with tumors with BRAF V600E/k mutations: Updated results from NCI-MATCH arm H.

3110Background: The NCI-MATCH precision medicine trial assigns patients (pts) with solid tumors, lymphomas or multiple myeloma to a targeted therapy based on genetic alterations identified in pretreatment biopsies. Arm H (EAY131-H) evaluated the combination of the BRAF inhibitor (inh) dabrafenib (DAB), and the MEK inh, trametinib (TRM), in pts with BRAF V600E/K mutations. Thirty-five pts in the primary cohort (PC) were enrolled from Jan 2016-Feb 2018, with 30 patients included in the primary efficacy analysis (1). The trial reactivated for an expansion cohort (EC) in October 2020. Methods: Pts could enroll based on molecular results from approved local CLIA labs; central confirmation was required to be included in primary efficacy analyses. Pts with melanoma, thyroid, or colorectal cancer were excluded. Pts with NSCLC were excluded after the US Food and Drug Administration (FDA) approved DAB/TRM in 2017. Pts received DAB 150 mg po BID and TRM 2 mg PO daily on 28-day cycles until disease progression or intolerable toxicity, with restaging every 2 cycles. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), 6-month (mo) PFS, and overall survival (OS). Results: An additional 9 pts were accrued to the EC; 6 pts were eligible, started treatment and molecularly confirmed. One pt never started therapy and 2 pts had inadequate tissue for central molecular confirmation, resulting in a combined cohort (CC) population of 36 pts. The trial closed to accrual in Jan 2023. In the CC, 17 different histologies were represented. In the EC, 38% of pts were female, with a median age of 60; > 50% had received at least 3 lines of prior therapy. In the 6 pts with central assay results, 1 pt with a pilocytic astrocytoma had a CR, with a PFS >18 mo and 1 pt with GBM had a PR, with a PFS of >12 mo. The 2 pts without central assay results had PRs, both were alive and free of progression for >7 mo. Median OS in the EC is 19.8 mo. For the CC, the confirmed ORR is 36.1% (90% CI 22.9-51.2%); the estimated 6 mo PFS is 67.6% (90% CI 54.5-80.8%). Median OS for the CC is 28.6 mo. At the time of data cutoff (Nov 2023) 2 pts in the PC and 1 pt in the EC are still on therapy. Adverse events were comparable to previously reported profiles of DAB/TRM. Conclusions: In this pretreated cohort of BRAF^V600 mutated solid tumors, the combination of DAB/TRM showed clinically meaningful activity with durable responses seen in pts across multiple histologies, further supporting the disease agnostic approval by the FDA for this regimen. 1. J Clin Oncol. 2020;38[33]. Clinical trial information: NCT04439292.

Duke Scholars

Author April Kelly Scott Salama Medicine, Medical Oncology