Novartis reports positive data from COMBI-d and COMBI-v studies

6th June 2019 (Last Updated June 6th, 2019 00:00)

Novartis has reported positive results from the Phase III COMBI-d and COMBI-v clinical trials that assessed a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) as first-line therapy for unresectable or metastatic BRAF-mutation-positive melanoma.

Novartis reports positive data from COMBI-d and COMBI-v studies
Novartis has entered an agreement to acquire AveXis Inc in an $8.7 billion deal Credit: Andrew Hecht

Novartis has reported positive results from the Phase III COMBI-d and COMBI-v clinical trials that assessed a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) as first-line therapy for unresectable or metastatic BRAF-mutation-positive melanoma.

Tafinlar is a BRAF inhibitor, while Mekinist is a mitogen-activated protein kinase (MEK) inhibitor. The combination improved overall and progression-free, long-term survival, with 34% of patients surviving after five years.

A prolongation in progression-free survival (PFS) was noted, and 19% of subjects treated with Tafinlar plus Mekinist did not display any signs of disease progression after five years.

Novartis chief medical officer and global drug development head John Tsai said: “The five-year COMBI-d/v analysis is truly gratifying, as it shows us that many BRAF+ melanoma patients on Tafinlar + Mekinist are living much longer than what may have been expected when originally diagnosed.”

Of the patients that experienced a complete response (CR) with the combination therapy, 19% were found to have five-year PFS and overall survival rates of 49% and 71%, respectively.

In the overall population, these five-year rates were 19% and 34%, respectively.

Adverse events (AE) occurred in 548 of 559 patients without any new safety signals. Out of the 559 patients, 99 discontinued treatment due to AEs.

The most common events were pyrexia, decreased ejection fraction and increased alanine aminotransferase. The investigators did not report any treatment-related deaths.

COMBI-d is a pivotal, randomised, double-blinded study that compared the combination therapy to Tafinlar alone and placebo in 422 patients suffering from unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma.

The two-arm, open-label COMBI-v trial compared the Tafinlar plus Mekinist combination to vemurafenib monotherapy in BRAF V600E/K mutation-positive unresectable or metastatic melanoma patients. The primary endpoint of the trial was overall survival.