GlaxoSmithKline reports positive overall survival results for Tafinlar, Mekinist combination in melanoma

GlaxoSmithKline announced Friday that the combination of the BRAF inhibitor Tafinlar (dabrafenib) and the MEK inhibitor Mekinist (trametinib) demonstrated a significant 29-percent reduction in the risk of death compared to Tafinlar alone in patients with BRAF V600E/K mutation-positive metastatic melanoma.

Patrick Vallance, president of pharmaceuticals R&D at the company, said "these final overall survival results from COMBI-d...further reinforce the scientific rationale for combining MEK and BRAF inhibitors." GlaxoSmithKline noted that completion of the study was a post-marketing requirement for the FDA's accelerated approval of the combination last year.

The Phase III trial randomised 423 patients with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma to receive the combination of Tafinlar and Mekinist or Tafinlar alone. An earlier analysis showed that treatment with the combination resulted in a 25-percent reduction in the risk of disease progression or death compared to Tafinlar alone. In addition, median progression-free survival, which was the study's primary endpoint, was 9.3 months in patients treated with Tafinlar and Mekinist compared to 8.8 months in patients given Tafinlar alone.

GlaxoSmithKline noted that the safety profile was consistent with that observed to date for the combination and no new safety concerns were observed. The company added that the final data from COMBI-d will be submitted to regulatory authorities for review in the coming months. Last year, the drugmaker withdrew a filing in Europe seeking approval of Mekinist in combination with Tafinlar for the treatment of adults with unresectable or metastatic melanoma with a BRAF V600 mutation. At the time, GlaxoSmithKline said it would resubmit the application when additional results from the COMBI-d study become available.

The combination of Mekinist and Tafinlar is also approved in Australia. Mekinist was in-licensed by GlaxoSmithKline in 2006 from Japan Tobacco, with the latter retaining co-promotion rights in Japan.

Last year, GlaxoSmithKline entered an agreement to divest its oncology products, including Tafinlar and Mekinist, to Novartis for $14.5 billion. The deal also includes $1.5 billion in milestone payments tied to results of the COMBI-d trial.

For related analysis, see ViewPoints: Can BRAF/MEK combinations fend of immuno-oncology threat in melanoma? and Physician Views Poll Results – Oncologists suggest Mekinist/Tafinlar combination will experience notable growth in melanoma over next 12 months.

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