Novartis receives positive CHMP opinion for Tafinlar® + Mekinist®

Novartis receives positive CHMP opinion for Tafinlar® + Mekinist®  in BRAF-positive non-small cell lung cancer (NSCLC) patients
Novartis today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of Tafinlar® (dabrafenib) in combination with Mekinist® (trametinib) to treat patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors 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[2], 1-3%, may be driven by the BRAF mutation[3].

”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 tumor 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, diarrhea, asthenia, decreased appetite, dry skin, chills, peripheral edema, cough and rash[1]. 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[4], and an estimated 1.8 million new cases of lung cancer are diagnosed each year[2]. Among patients with NSCLC, roughly 30% have an actionable mutation that may be targeted with available therapies[5],[6],[7],[8].  To determine that treatment, medical organizations recommend genetic testing for patients with lung cancer[9].

[1] Planchard D et al. Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: An open-label, multicentre Phase II trial. 2016. Lancet Oncol 17: 984-93.
[2] World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Lung Cancer. Available at Accessed February 2, 2017.
[3] Pao W, Girard N. New driver mutations in non-small-cell lung cancer. 2011. Lancet Oncol 12: 175-180.
[4] World Health Organization. Estimated number of deaths, both sexes, worldwide in 2012. World Health Organization. Accessed on January 19, 2017.
[5] Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Cancer Management: Novel Targets and Recent Clinical Advances. Clinical Advances in Hematology & Oncology. 2012; 10: 226-224.
[6] Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12:175-180.
[7] Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of Patients With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin Oncol. 2011;29:2046-2051.
[8] Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nature. 2012;378-381.
[9] Lindeman, N.I., et al. Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors. Arch Pathol Lab Med. 2013; 137: 828-1174.