Nilotinib Plus Dabrafenib/Trametinib in Metastatic Melanoma

Inclusion Criteria:

Patients must have histologically confirmed metastatic or unresectable melanoma
Patients must have a BRAF V600 mutation
Patients must have failed any BRAFi/MEKi regimen to qualify for the trial
Age ≥18 years
ECOG performance status ≤ 1
Patients must have adequate organ and marrow function
Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
HBV viral load must be undetectable on suppressive therapy, if indicated.
Patients must have an undetectable HCV viral load.
Patients with treated brain metastases are eligible if follow-up brain imaging 4 weeks or longer after central nervous system (CNS)-directed therapy shows no evidence of progression.
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment
women of childbearing potential and men must agree to use adequate contraception
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Patients with chronic hypokalemia or chronic hypomagnesemia
Patients with long QT syndrome or baseline QTc (Fridericia) >470 msec in males and >480 msec in females
Patients who are receiving any other investigational therapies that could affect the primary or secondary outcomes of this study
Untreated brain metastases
History of allergic reactions attributed to compounds of similar chemical or biologic composition to nilotinib, dabrafenib, and trametinib.
Patients receiving any medications or substances that are strong CYP3A or CYP2C8 inhibitors or substances that are strong CYP3A inducers
Use of Proton pump inhibitors concurrent with nilotinib
Use of drugs or substances known to prolong QT interval is prohibited with Nilotinib
Patients with uncontrolled intercurrent illness.
Patients with psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant or lactating women
Other prior malignancy active within 2 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanoma carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast that has/have undergone curative surgery or radiation