Tafinlar (dabrafenib) + Mekinist (trametinib) success in COMBI-d trial for BRAF V600E/K mutation-positive metastatic melanoma- Novartis

Novartis announced data from the Phase III COMBI-d study showing a significant survival benefit for patients with BRAF V600E/K mutation-positive metastatic melanoma when treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) compared to Tafinlar monotherapy alone. This is the first combination of BRAF/MEK inhibitors to demonstrate a statistically significant overall survival benefit for this patient population in two Phase III studies. Results are being presented today at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

The final analysis included the 423 patients enrolled in COMBI-d and showed that the combination of Tafinlar and Mekinist achieved a statistically significant overall survival (OS) benefit compared to Tafinlar monotherapy (median of 25.1 months vs 18.7 months). The analysis for the combination also showed median progression-free survival (PFS) of 11.0 months, overall response rate (ORR) of 69%, and median duration of response (DoR) of 12.9 months. The safety results were consistent with the profile observed to date for the combination and consistent with the profile observed for Tafinlar monotherapy; no new safety concerns were observed. The most common adverse events (>=20%) in the combination arm were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, joint pain (arthralgia), hypertension, vomiting, cough and peripheral edema.

Comment: The combination is approved in the US but the CHMP of EMA has indicated that the data provided to date did not allow the Committee to conclude on a positive benefit-risk balance of the combination. Novartis ( as successor to GSK) intends to re-submit the MAA for the combined use of Tafinlar and Mekinist with additional data from the Phase III programme.