Nilotinib Plus Dabrafenib/Trametinib or Encorafenib/Binimetinib in Metastatic Melanoma

Inclusion Criteria

• •3.1.1 Patients must have histologically confirmed metastatic or unresectable melanoma.
• •Radiological evaluation should occur within 28 days prior to enrollment initiation.
• •3.1.2 Patients must have a BRAF V600 mutation. Any CLIA-certified mutation testing is acceptable to document mutation status.
• •3.1.3 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.
• •3.1.4 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.
• •3.1.5 Age ≥18 years.
• •3.1.6 ECOG performance status ≤ 1. See Appendix A.
• •3.1.7 Patients must have adequate organ and marrow function as defined below: absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2 (see Appendix B)
• •3.1.8 Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• •3.1.9 For patients with known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• •3.1.12 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.
• •3.1.13 Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• •3.1.14 Measurable (target) disease by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Target lesions selected for tumor measurements should be those where additional (e.g., palliative) treatments are not indicated or anticipated.
• •Measurable disease per RECIST 1.1 requirements: defined as longest diameter to be recorded for non-nodal lesions \> 10mm and short axis for nodal lesions \>15 mm using conventional techniques For patients enrolling onto the study with stable disease, it is possible they have no evidence of disease and/or do not have disease that meet RECIST 1.1 criteria if they have had clinical and radiographical response to treatment. This will be noted and monitored on subsequent surveillance imaging as per guidelines.
• •3.1.15 The effects of nilotinib, encorafenib, dabrafenib, binimetinib and trametinib on the developing human fetus are unknown, women of childbearing potential and men must agree to use adequate contraception (non-hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of nilotinib, dabrafenib, and trametinib administration.
• •3.1.16 Patients must have the ability to understand and the willingness to sign a written informed consent document.