Study of the Anti-PD-1 Antibody Nivolumab in Combination With Dabrafenib and/or Trametinib

Patients are being asked to take part in this clinical research study because they have BRAF- or NRAS-mutated metastatic melanoma. If they participate they will receive the investigational drug nivolumab in combination with dabrafenib and/or trametinib based on their medical diagnosis, BRAF V600 test results and/or NRAS-mutated status. The research study will evaluate the safety and efficacy of the two drugs nivolumab and dabrafenib or nivolumab and trametinib. Once this is evaluated, then additional subjects will be enrolled for treatment with the triplicate (all 3 drugs) of nivolumab, dabrafenib and trametinib together. A treatment cycle will be 28 days, coinciding with the administration of nivolumab. The DLT evaluation period will be restricted to cycle 1, although toxicities in subsequent cycles will be closely evaluated. In trametinib-containing arms, a loading dose will be given on days 1 and 2 of cycle 1 to allow steady state concentrations to be achieved within one week of administration. In the absence of treatment delays due to adverse event(s), treatment may continue for 3 years or until one of the following criteria applies: * Disease progression * Intercurrent illness that prevents further administration of treatment * Unacceptable adverse event(s) * Patient decides to withdraw from the study * General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator Patients will be considered evaluable for toxicity if they receive 1 complete cycle of therapy, or if they experience dose limiting toxicities (DLTs). Definition of DLTs include: * Any Grade 2 drug-related uveitis or eye pain or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment * Any Grade 3 non-skin, drug-related adverse event lasting \> 7 days, with the following exceptions for drug-related laboratory abnormalities, uveitis, pneumonitis, bronchospasm, diarrhea, colitis, neurologic adverse event, hypersensitivity reactions, and infusion reactions * Grade 3 drug-related uveitis, pneumonitis, bronchospasm, diarrhea, colitis, neurologic adverse event, hypersensitivity reaction, or infusion reaction of any duration requires discontinuation * Grade 3 drug-related laboratory abnormalities do not require treatment discontinuation except the following: Grade 3 drug-related thrombocytopenia \> 7 days or associated with bleeding requires discontinuation; Any drug-related liver function test (LFT) abnormality that meets the following criteria require discontinuation - AST or ALT \> 8 x ULN; Total bilirubin \> 5 x ULN; Concurrent AST or ALT \> 3 x ULN and total bilirubin \> 2 x ULN; * Any Grade 4 drug-related adverse event or laboratory abnormality, except for the following events which do not require discontinuation: * Isolated Grade 4 amylase or lipase abnormalities that are not associated with symptoms or clinical manifestations of pancreatitis and decrease to \< Grade 4 within 1 week of onset. * Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with clinical sequelae and are corrected with supplementation/appropriate management within 72 hours of their onset * Any dosing interruption lasting \> 6 weeks with the following exceptions: * Dosing interruptions to allow for prolonged steroid tapers to manage drug-related adverse events are allowed. Prior to re-initiating treatment in a subject with a dosing interruption lasting \> 6 weeks, the Investigator must be consulted. Tumor assessments should continue as per protocol even if dosing is interrupted * Dosing interruptions \> 6 weeks that occur for non-drug-related reasons may be allowed if approved by the Investigator. Prior to re-initiating treatment in a subject with a dosing interruption lasting \> 6 weeks, the Investigator must be consulted. Tumor assessments should continue as per protocol even if dosing is interrupted Any adverse event, laboratory abnormality, or intercurrent illness which, in the judgment of the Investigator, presents a substantial clinical risk to the subject with continued nivolumab dosing. Patients will be followed for 2 years after removal from study or until death, whichever occurs first, through standard of care visits or by medical records review. Patients removed from study for unacceptable adverse event(s) will be followed until resolution or stabilization of the adverse event.