Phase III COMBI-AD trial of Tafinlar + Mekinist shows benefits for relapse free survival in melanoma.- Novartis.

Novartis announced a new data analysis of COMBI-AD, a phase III multi-center study evaluating Tafinlar (dabrafenib) in combination with Mekinist (trametinib) in stage III adjuvant resected BRAF V600-mutant melanoma. With extended study follow up, Tafinlar in combination with Mekinist continued to show more than 50% risk reduction in relapse free survival (RFS) versus placebo in patients with resected BRAF V600-mutant stage III melanoma. The updated COMBI-AD data was also used to generate a statistical cure-rate model that estimated the fraction of patients who may not relapse. The cure rate was 54% in the Tafinlar + Mekinist arm compared to 37% in the placebo arm. In the phase III COMBI-AD global study, at median follow-ups of 44 months (Tafinlar + Mekinist) and 42 months (placebo), the three- and four-year RFS rates were 59% and 54% in the Tafinlar + Mekinist arm and 40% and 38% in the placebo arm, respectively.

RFS was also analyzed by subgroups defined by baseline disease stage by the American Joint Committee on Cancer 7th and 8th editions and included nodal metastatic burden, and ulceration status. A cure rate model estimated that the fraction of patients who may not relapse was 54% in the Tafinlar + Mekinist arm compared with 37% in the placebo arm. The fraction of patients remaining relapse free long term was estimated using a Weibull mixture cure-rate model. No updated safety analysis was performed as all patients have completed treatment at the time of the updated RFS analysis. These data were presented at the European Society of Medical Oncology.