GSK announces start of Phase III programme for combination of dabrafenib (GSK2118436) and trametinib (GSK1120212) in BRAF V600 mutation-positive metastatic cutaneous melanoma

Issued: London UK

GlaxoSmithKline plc. today announced the start of a Phase III programme evaluating the combination of dabrafenib, its BRAF inhibitor, and trametinib, its MEK inhibitor, in patients with BRAF mutation-positive metastatic cutaneous melanoma. The studies comprising the programme are:

• COMBI-d (Combination of MEK and BRAF Inhibitors versus dabrafenib), a Phase III trial of the combination of its MEK inhibitor, trametinib, and its BRAF inhibitor, dabrafenib, in patients with BRAF V600E or V600K mutation-positive metastatic cutaneous melanoma. This global trial will evaluate whether combining the two investigational agents is better than dabrafenib single-agent therapy in stopping or slowing the progression of metastatic melanoma (Progression Free Survival).
• COMBI-v (Combination of MEK and BRAF Inhibitors versus vemurafenib), a Phase III trial of the combination of its MEK inhibitor, trametinib, and its BRAF inhibitor, dabrafenib, in patients with BRAF V600E or V600K mutation-positive metastatic cutaneous melanoma. This global trial will evaluate whether combining the two investigational agents is better than single-agent therapy with vemurafenib, an approved BRAF inhibitor, in improving the overall survival of patients with metastatic melanoma (Overall survival).
• Both studies will evaluate the safety profile of the dabrafenib-trametinib combination.

“While recent clinical findings with BRAF inhibitors in melanoma have shown significant improvement over chemotherapy, eventually tumours become resistant to these inhibitors leading to disease relapse. Recent scientific advances have led us to the hypothesis that the combination of BRAF and MEK inhibitors may delay resistance” said Dr. Rafael Amado, Head of Oncology R&D for GlaxoSmithKline. “Guided by promising results from an early phase study, we are launching this Phase III programme and will continue discussions with regulators about the future regulatory pathway for the combination.”

About COMBI-d: GSK study MEK115306 (NCT01584648) is a Phase III, randomised, double-blinded study comparing the combination of the BRAF inhibitor, dabrafenib, and the MEK inhibitor, trametinib, to dabrafenib and placebo as first-line therapy in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. The primary endpoint of the study is progression-free survival and patients will be followed for overall survival. The study seeks to enrol about 340 patients from investigative sites in the US, Europe, Canada, Russia, Ukraine, Argentina, and Australia.

About COMBI-v: GSK study MEK116513 (NCT01597908) is a Phase III, randomised, open-label study comparing the combination of the BRAF inhibitor, dabrafenib, and the MEK inhibitor, trametinib, to the BRAF inhibitor vemurafenib in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. The primary endpoint of the study is overall survival. The study seeks to enrol about 690 patients from investigative sites in the US, Europe, Canada, Russia, Ukraine, Israel, Argentina, Brazil, Korea, New Zealand, Taiwan, and Australia.

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GlaxoSmithKline cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk factors' in the 'Financial review & risk' section in the company's Annual Report 2011 included as exhibit 15.2 to the company's Annual Report on Form 20-F for 2011.