GlaxoSmithKline (GSK) has released positive results from a Phase III trial showing that the Tafinlar-Mekinist combination drug has met its primary endpoint of progression free survival (PFS) in patients with BRAF V600 E or K mutation positive unresectable or metastatic melanoma.
In the trial, the combination drug of Tafinlar (dabrafenib) and Mekinist (trametinib) was compared with single agent therapy with Tafinlar in these patients.
Compared with those in the Phase I/II study, PFS, response rate and interim overall survival results for the combination drug were seen to be consistent.
In the Phase III trial, PFS observed among patients in the single agent dabrafenib arm was greater than that seen in previous single agent dabrafenib studies, leading to a more modest difference in PFS between treatment arms than was observed in the Phase I/II trial.
The most commonly reported adverse events in the combination drug were pyrexia, fatigue, nausea, headache, chills, diarrhoea, arthralgia, rash, hypertension, and vomiting.
GSK senior vice-president of oncology R&D Rafael Amado said: "These results, along with data we expect to receive later in the year from our Phase III study comparing the combination to vemurafenib, will increase the body of evidence on the safety and efficacy of this combination in appropriate patients with melanoma."
The Phase III trial of the combination drug in BRAF V600E/K metastatic melanoma includes two studies: COMBI-d and COMBI-v.
Results were based on COMBI-d 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 patients with unresectable or metastatic 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.
A total of 423 patients from investigative sites in Australia, Europe, North and South America were randomised in the study.
The randomised, open-label COMBI-v study compared the combination of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib to the BRAF inhibitor vemurafenib in patients with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma and its primary endpoint is overall survival.
The COMBI-v study results are likely to be announced in 2014.
Image: Melanoma on a patient’s skin. Photo: courtesy of Jmh649.