GlaxoSmithKline announced that the Independent Data Monitoring Committee (IDMC) recommended COMBI-v (MEK116513), a phase III study of its MEK inhibitor, trametinib (Mekinist), in combination with its BRAF inhibitor, dabrafenib (Tafinlar), compared to vemurafenib in patients with BRAF V600E or V600K mutation-positive unresectable or metastatic cutaneous melanoma be stopped early.

This IDMC recommendation is based on an interim analysis which demonstrated an overall survival benefit for the trametinib and dabrafenib combination compared to vemurafenib that crossed the pre-specified efficacy stopping boundary. The safety profile of the trametinib and dabrafenib arm was consistent with the safety profile of the combination observed to date.

The IDMC recommendation is based on headline data; further analysis of safety and efficacy data is underway and will be completed in the coming months. Eligible study patients who were randomised to the vemurafenib arm will be allowed to cross over to receive treatment with the trametinib and dabrafenib combination.

Dr. Rafael Amado, Head of Oncology R&D at GSK, said: “Today’s headline results for the combination of dabrafenib and trametinib add to the body of evidence our phase III programme has provided thus far, which we hope will more fully characterise the efficacy and safety profile of this combination for patients with BRAF V600-mutant metastatic melanoma. We will continue to analyse this data versus vemurafenib over the coming months and look forward to sharing these with the scientific community once the analysis is complete.”  

This phase III, randomised, open-label study compared the combination of dabrafenib and trametinib to vemurafenib in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. COMBI-v enrolled 704 patients from investigative sites in the US., Europe, Canada, Russia, Ukraine, Israel, Argentina, Brazil, Korea, New Zealand, Taiwan, and Australia.

The primary objective of the study was to evaluate dabrafenib and trametinib combination therapy vs. vemurafenib with respect to OS. Secondary objectives evaluated and compared dabrafenib and trametinib combination therapy versus vemurafenib with respect to progression-free survival, overall response rate, and duration of response. The safety of dabrafenib and trametinib combination therapy, including incidences of squamous cell carcinoma and other proliferative skin diseases, was also evaluated.

Cutaneous melanoma is the most aggressive form of all skin cancers. Worldwide, it is expected that over 132,000 people will be diagnosed with melanoma each year and more than 37,000 people are expected to die of this tumour disease annually. In the US and most countries of the Western World including Australia, the incidence of melanoma continues to rise faster than any other type of cancer in men and the annual increase in the incidence of melanoma in women is second only to lung cancer.

Combination use of trametinib and dabrafenib in patients with unresectable or metastatic melanoma who have BRAF V600E or K mutation is approved only in the US and Australia.

Trametinib was in-licenced by GSK in 2006 from Japan Tobacco Inc. (JTI). GSK holds the worldwide exclusive rights to develop, manufacture, and commercialise trametinib, while JTI retains co-promotion rights in Japan.

Tafinlar and Mekinist are registered trademarks of the GSK group of companies.

GSK one of the world’s leading research-based pharmaceutical and healthcare companies is committed to improving the quality of human life by enabling people to do more, feel better and live longer.