GlaxoSmithKline starts Phase III study to test combined BRAF/MEK inhibition in patients with BRAF positive melanoma following surgery

GlaxoSmithKline plc. today announced the start of COMBI-AD, a Phase III study evaluating the combination of dabrafenib, its BRAF inhibitor and trametinib, its MEK inhibitor as adjuvant therapy for melanoma. This global study will investigate whether combining the two investigational agents can delay or prevent the recurrence of melanoma (Relapse Free Survival) in patients with Stage IIIa, IIIb, or IIIc BRAF V600E or V600K mutation-positive melanoma that has been completely removed by surgery. The study will also evaluate the safety profile of the dabrafenib-trametinib combination in this treatment setting.

“The patients included in this trial are at high risk of their melanoma returning after surgery and there are currently few treatment options to reduce this risk” said Dr. Rafael Amado, Head of Oncology R&D for GlaxoSmithKline. “Given the efficacy and safety findings observed with combined dabrafenib-trametinib treatment in the metastatic setting, we are investigating whether the combination administered after surgery can help these patients live longer without melanoma recurrence.”

Two Phase III studies of combined dabrafenib-trametinib are ongoing in the metastatic BRAF V600 melanoma setting. (NCT01584648 and NCT01597908)

COMBI-AD: Study 115532 (NCT01682083) is a Phase III, randomised, double-blinded study comparing the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor, trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (sentinel lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma will be screened for eligibility. Subjects will be randomised to receive either dabrafenib (150mg, twice daily) and trametinib (2mg, once daily) combination therapy or two placebos for 12 months. The primary endpoint of the study is relapse-free survival. The study seeks to enrol about 850 subjects from more than 200 investigative sites across the world.

About dabrafenib

Dabrafenib is an investigational, orally bioavailable inhibitor of the BRAF protein. Dabrafenib was discovered and developed at GSK. EU and US regulatory submissions for dabrafenib as a monotherapy treatment for BRAF V600 mutation-positive metastatic melanoma (150 mg once daily) were announced in August 2012. Global submissions are ongoing.

About trametinib

Trametinib is an investigational, orally bioavailable inhibitor of the MEK protein discovered by Japan Tobacco, Inc and in-licensed by GSK in 2006. Submission of a New Drug Application in the US for trametinib as a monotherapy treatment for BRAF V600 mutation-positive metastatic melanoma (2 mg once daily) was announced in August 2012. Submissions in the EU and other regions will follow in the coming months.