The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of Novartis' Tafinlar (dabrafenib) in combination with Mekinist (trametinib) to treat patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours express the BRAF V600 mutation.

If approved, Tafinlar + Mekinist will be the first targeted treatment available for patients with BRAF V600-positive NSCLC. Of the estimated 1.8 million new cases of lung cancer diagnosed worldwide each year, 1-3%, may be driven by the BRAF mutation.

“At Novartis, we are committed to finding treatments for rare cancers with an unmet need. Today’s CHMP opinion marks a major milestone for NSCLC patients with the BRAF V600 mutation, who have very limited treatment options,” said Bruno Strigini, CEO, Novartis Oncology. “We welcome the CHMP’s opinion as a first step towards that goal, and look forward to continuing to work with European health authorities to make Tafinlar + Mekinist available for appropriate NSCLC patients.”

The positive CHMP opinion was based on safety and efficacy data from a Phase II study of Tafinlar + Mekinist in patients with BRAF V600-positive NSCLC (36 treatment-naïve and 57 previously treated with chemotherapy).

The 57 patients who had tumour progression on at least one platinum based chemotherapy, receiving 150 mg of Tafinlar twice daily and 2 mg of Mekinist once daily, demonstrated an overall response rate (ORR) of 63.2% (95% confidence interval [CI], 49.3%, 75.6%) and duration of response of 9.0 months (95% CI, 6.9, 18.3 months). The most common adverse events (incidence >20%) were pyrexia, nausea, vomiting, diarrhoea, asthenia, decreased appetite, dry skin, chills, peripheral edema, cough and rash. Updated data from the previously treated and treatment-naïve cohorts were included in the overall data package for EMA review and will also be presented at upcoming medical meetings.

The European Commission (EC) typically adheres to the recommendation of the CHMP and usually delivers its final decision within two months. The decision will be applicable to all 28 European Union (EU) member states plus Iceland and Norway. In Europe, Tafinlar and Mekinist is approved for the treatment of patients with unresectable or metastatic melanoma who have a BRAF V600 mutation.

The US Food and Drug Administration (FDA) granted Tafinlar + Mekinist Breakthrough Therapy Designation for advanced or metastatic BRAF V600-positive NSCLC patients in 2015 and Priority Review in November 2016. Combination use of Tafinlar + Mekinist is also approved in the US, Australia, Canada and additional countries for patients with unresectable or metastatic melanoma whose tumors tested positive for the BRAF V600 mutation.

Worldwide, lung cancer causes more deaths than colon, breast, and prostate cancer combined, and an estimated 1.8 million new cases of lung cancer are diagnosed each year. Among patients with NSCLC, roughly 30% have an actionable mutation that may be targeted with available therapies.  To determine that treatment, medical organizations recommend genetic testing for patients with lung cancer.

Novartis Oncology’s research into targeted therapies has helped transform treatment approaches for patients living with mutation-driven types of lung cancer. Patients with a mutation-driven NSCLC may be candidates for treatment with targeted therapies.

Novartis continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds that target genetic biomarkers in NSCLC.

Combination use of Tafinlar + Mekinist in patients with unresectable or metastatic melanoma who have a BRAF V600 mutation is approved in the US, EU, Australia, Canada and other countries.

Tafinlar and Mekinist target different kinases within the serine/threonine kinase family - BRAF and MEK1/2, respectively - in the RAS/RAF/MEK/ERK pathway, which is implicated in non-small cell lung cancer (NSCLC) and melanoma, among other cancers. When Tafinlar is used with Mekinist, the combination has been shown to slow tumor growth more than either drug alone. The combination of Tafinlar + Mekinist is currently being investigated in an ongoing clinical trial program across a range of tumour types conducted in study centres worldwide.

The safety and efficacy profile of the Tafinlar + Mekinist combination has not yet been established outside of the approved indications.

Tafinlar and Mekinist are also indicated in more than 40 countries worldwide, including the US and EU, as single agents to treat patients with unresectable or metastatic melanoma with a BRAF V600 mutation.