"Today's approval represents an important milestone for the lung cancer community, especially those patients living with the BRAF V600 mutation who previously had few options," said Bruno Strigini, CEO, Novartis Oncology. "At Novartis we are committed to bringing meaningful scientific advances that fill critical unmet needs to patients."
Today's EU approval follows a positive opinion granted in February by the Committee for Medicinal Products for Human Use (CHMP), which was based on safety and efficacy of dabrafenib in combination with trametinib in a Phase II, three-cohort, multicenter, non-randomised and open-label study in which patients with stage IV BRAF V600E mutant NSCLC were enrolled (36 treatment-naïve [previously untreated] and 57 previously treated with chemotherapy).
For the primary endpoint of investigator-assessed overall response rate (ORR), 36 treatment-naïve patients receiving 150 mg of Tafinlar twice daily and 2 mg of Mekinist once daily demonstrated an ORR of 61.1% (95% confidence interval [CI]: 43.5%, 76.9%). In this population, 68% of patients had not progressed after 9 months. The median duration of response (DoR) and progression free survival (PFS) in the previously untreated population were not yet reached at the time of approval. In the previously treated population receiving the same dosage, patients demonstrated an ORR of 66.7% (95% CI: 52.9%, 78.6%). The response was durable with a median DoR reaching 9.8 months (95% CI: 6.9, 16.0). An in-depth analysis of data from the treatment-naïve cohort will be presented at an upcoming medical meeting.
The most common adverse events (incidence >20%) were pyrexia, nausea, vomiting, peripheral edema, diarrhea, dry skin, decreased appetite, asthenia, chills, cough, fatigue, rash, and dyspnoea.
The US Food and Drug Administration (FDA) granted Tafinlar + Mekinist Breakthrough Therapy designation for advanced or metastatic BRAF V600E-positive NSCLC patients in 2015 and Priority Review in November 2016. Combination use of Tafinlar + Mekinist is also approved in the US, Europe, Australia, Canada, and additional countries for patients with unresectable or metastatic melanoma whose tumors tested positive for the BRAF V600 mutation.
Novartis Commitment to Lung Cancer
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 biomarker 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 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.
About Tafinlar + Mekinist Combination
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 additional countries. The combination of Tafinlar and Mekinist is also approved for the treatment of advanced non-small cell lung cancer with a BRAF V600 mutation in Europe.
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 tumor types conducted in study centers 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.
Please see full Prescribing Information for Tafinlar and Mekinist.
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world.
1. Tafinlar® (dabrafenib) + Mekinist® (trametinib) Summary of Product Characteristics.
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