Nilotinib + BRAF/MEK Inhibitor Therapy

Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) or encorafenib (450 mg PO) and binimetinib (45 mg PO BID) on day one and will continue for 28 days. After 7 days, nilotinib will be added at 100mg PO BID and will continue for 21 days. For each subsequent cycle, nilotinib will be given for 28 days.

Patients will begin dabrafenib (150mg PO BID) and trametinib (2mg PO once daily) or encorafenib (450 mg PO) and binimetinib (45 mg PO BID) on day one and will continue for 28 days. After 7 days, nilotinib will be added at 200mg PO BID and will continue for 21 days. For each subsequent cycle, nilotinib will be given for 28 days.

This is a phase 1 dose-escalation study of nilotinib in combination with a fixed-dose of dabrafenib and trametinib or with encorafenib and binimetinib. The first week, patients will be treated with dabrafenib (150mg, twice daily) and trametinib (2mg, once daily), or encorafenib (450 mg, daily) and binimetinib (45 mg twice daily).

This is a phase 1 dose-escalation study of nilotinib in combination with fixed-dose dabrafenib and trametinib regimen for patients with metastatic or unresectable melanoma carrying a BRAF V600 mutation and have relapsed on a BRAF/MEK inhibitor therapy.

The goal is to assess the toxicity and tolerability and determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of the combination of nilotinib with dabrafenib and trametinib or with encorafenib and binimetinib. Additionally, this study will assess pharmacokinetic parameters of dabrafenib and nilotinib when used in combination.

Registro actualizado en ClinicalTrials.gov →

• 1.1 Patients must have histologically confirmed metastatic or unresectable melanoma.
• Radiological evaluation should occur within 28 days prior to enrollment initiation.
• 1.2 Patients must have a BRAF V600 mutation. Any CLIA-certified mutation testing is acceptable to document mutation status.
• 1.3 Patients must have stable disease on dabrafenib and trametinib or on encorafenib and binimetinib for a duration of greater than or equal to 3 months OR have failed any BRAFi/MEKi regimen to qualify for the trial, including the dabrafenib/trametinib combination and/or the encorafenib/ binimetinib combination.
• 1.4 Patient may have had prior immunotherapy for metastatic disease or prior cellular therapy (although NOT mandatory). NOTE: Other prior therapies are not allowed, with the exception of radiation.
• 1.6 ECOG performance status ≤ 1. See Appendix A.

Criterios de inclusión tal como figuran en el registro, recortados. La lista completa, con las exclusiones, está en el registro actualizado.