FDA Accepts sNDA, Grants Priority Review to Adjuvant Dabrafenib/Trametinib in BRAF V600E/K Mutation–Positive Melanoma
On December 22, the U.S. Food and Drug Administration (FDA) accepted a supplemental New Drug Application (sNDA) and granted Priority Review designation to dabrafenib (Tafinlar) in combination with trametinib (Mekinist) for the adjuvant treatment of patients with stage III melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, following complete resection. In October, the FDA also granted Breakthrough Therapy designation to dabrafenib in combination with trametinib for the adjuvant treatment of patients with stage III melanoma with a BRAF V600 mutation following complete resection.
“The FDA's decision to grant dabrafenib in combination with trametinib Breakthrough Therapy designation and Priority Review designation validates the potential of the combination to have a significant impact on the lives of melanoma patients treated in the adjuvant setting,” said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. “There remains a need to address the high risk of recurrence seen in these patients and improve the quality of care they receive.”
COMBI-AD
The Priority Review designation is based on results from COMBI-AD, a phase III study evaluating dabrafenib plus trametinib in patients with stage III BRAF V600E/K mutation–positive melanoma after complete resection. The study met its primary endpoint by significantly reducing the risk of disease recurrence or death by 53% vs placebo (hazard ratio [HR] = 0.47, 95% confidence interval [CI] = 0.39–0.58).
The combination treatment group also showed an improvement in the key secondary endpoint of overall survival (HR = 0.57, 95% CI = 0.42–0.79; P = .0006, which did not cross the predefined interim analysis boundary of P = .000019 to claim statistical significance). Other secondary endpoints where the combination demonstrated a clinically meaningful benefit include distant metastasis–free survival (HR = 0.51, 95% CI = 0.40–0.65) and freedom from recurrence (HR = 0.47, 95% CI = 0.39–0.57).
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
