The US Food and Drug Administration (FDA) has accepted Novartis' supplemental New Drug Application (sNDA) for filing, and granted Priority Review designation for Tafinlar (dabrafenib) in combination with Mekinist (trametinib) 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 Tafinlar in combination with Mekinist for the adjuvant treatment of patients with stage III melanoma with a BRAF V600 mutation following complete resection.
"The FDA's decision to grant Tafinlar in combination with Mekinist 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."
Priority Review designation is based on results from COMBI-AD, a phase III study evaluating Tafinlar + Mekinist 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% versus 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 OS (HR: 0.57 [95% CI: 0.42-0.79] p=0.0006, which did not cross the predefined interim analysis boundary of p=0.000019 to claim statistical significance). Other secondary endpoints where the combination demonstrated a clinically meaningful benefit include DMFS (HR: 0.51 [95% CI: 0.40-0.65]), and FFR (HR: 0.47 [95% CI: 0.39-0.57]).
According to FDA guidelines, treatments that receive Priority Review designation are those that address a serious or life threatening disease or condition and, if approved, would provide a significant improvement in treatment safety or efficacy. If a treatment is granted Priority Review designation, the goal of the FDA is to issue a decision within six months of application submission, rather than ten months for standard review.
Tafinlar in combination with Mekinist is currently approved in the US for patients with unresectable or metastatic melanoma with a BRAF V600E/K mutation as detected by an FDA-approved test and non-small cell lung cancer (NSCLC) with a BRAF V600E mutation.