GSK releases headline results of Phase III Tafinlar-Mekinist combination trial
Source: PBR (pharmaceutical-business-review.com), January 2014
GlaxoSmithKline has reported headline results of a Phase III trial of the Tafinlar (dabrafenib)-Mekinist (trametinib) combination, compared to single agent therapy with Tafinlar in patients with BRAF V600 E or K mutation positive unresectable or metastatic melanoma.
The company said that the trial met its primary endpoint of Progression Free Survival (PFS) and it follows the recent accelerated approval of the combined therapy in the US.
PFS, response rate and interim overall survival results for the combination drug were consistent compared to those seen in the Phase I/II study.
According to the company, in the Phase III study, 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.
In the combination arm, the most commonly observed adverse events were pyrexia, fatigue, nausea, headache, chills, diarrhoea, arthralgia, rash, hypertension and vomiting.
GSK senior vice president Oncology R&D Rafael Amado said the company is happy to report that the first of the company’s Phase III studies investigating the combination of Tafinlar and Mekinist met its primary endpoint.
“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," Amado said.
The Phase III trial for dabrafenib and trametinib in BRAF V600E/K metastatic melanoma includes two studies: COMBI-d (also known as MEK MEK115306) and COMBI-v (also known as MEK116513).
COMBI-d study compared the combination of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib to dabrafenib and placebo as first-line therapy in patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma and its primary endpoint is progression-free survival and patients will be followed for overall survival.
About 423 patients from investigative sites in Australia, Europe, North and South America were randomized in this phased of the trial.
The 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 (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma and its primary endpoint is overall survival and results are anticipated in 2014.