Follow-up treatment with dabrafenib and/or trametinib following a prior clinical trial for cancers with a BRAF V600 mutation

The BRAF V600 mutation is a change in the BRAF gene that causes a specific signaling pathway in the cells (the MAPK signaling pathway) to remain permanently activated. This can promote uncontrolled cell growth and thus fuel tumor growth. This mutation, along with other genetic alterations, can occur in various types of cancer, including melanoma, non-small-cell lung cancer, and rare tumors such as high-grade gliomas. The two study drugs are targeted therapies. Dabrafenib (brand name: Tafinlar) is a BRAF inhibitor that specifically blocks the altered BRAF protein. Trametinib (brand name: Mekinist) is a MEK inhibitor that blocks another protein in the same signaling pathway. This is intended to slow down uncontrolled cell growth. Dabrafenib and trametinib are already approved, either alone or in combination, for certain cancers with the BRAF V600 mutation. The combination is approved, among other indications, for certain forms of melanoma and non-small-cell lung cancer. For BRAF V600E-mutated high-grade gliomas, the combination is approved for children aged 1 year and older; for adult patients in this situation, there is currently no approval for either monotherapy or combination therapy. Dabrafenib is taken twice daily as a capsule, and trametinib once daily as a tablet.

The goal of this Phase 4 study is to enable patients who were treated with dabrafenib and/or trametinib in a previous clinical trial to continue treatment, while assessing long-term safety and tolerability. The study is open-label (not blinded), which means that both the medical staff and the patients know which medication is being administered. Depending on their prior treatment, patients will receive either dabrafenib alone, trametinib alone, or a combination of both active ingredients. The study is designed to last up to approximately 10 years. It may end earlier if the treatment becomes routinely available and reimbursable or if another access program is established.

Patients aged 18 and older who are currently being treated with dabrafenib and/or trametinib as part of a previous study by Novartis or GSK and who, in the opinion of the study physicians, are likely to continue to benefit from the treatment are eligible to participate in the study. Patients must be able to meet the study requirements and must not have permanently discontinued treatment in the prior study. Participation is also not possible if dabrafenib and/or trametinib are routinely available and covered by insurance for the respective cancer in the patient’s home country.