Inclusion Criteria: 

• Able to provide written informed consent. Adult patients under guardianship may participate if permitted by local regulations with the consent of their legally authorized guardian. All local regulations concerning patients under guardianship must be followed.
• Age ≥ 18 years at the time of informed consent.
• Histologically confirmed diagnosis of cutaneous melanoma with metastases to the brain.
• Presence of BRAFV600 mutation in tumor tissue previously determined by a local PCR or NGS-based assay at any time prior to Screening or by a central laboratory during Screening.
• Patients are required to submit archival or fresh tumor tissue and a blood sample prior to enrollment. Tissue samples will be used to determine BRAFV600-mutation status by central laboratory.
• Must have at least 1 parenchymal brain lesion ≥ 0.5 cm and ≤ 4 cm, defined as an MRI contrast-enhancing lesion that may be accurately measured in at least 1 dimension. Note: Measurable intracranial lesions that have been previously irradiated and have not been shown to be progressing following irradiation should not be considered as target lesions.
• Patients may have received the following prior therapies.

Safety Lead-in, Phase 2 Randomized, Phase 2 Arm A Cohort 1:

• May have received prior local therapy for brain metastases including but not restricted to brain surgery, whole brain radiotherapy (WBRT), stereotactic radiotherapy or stereotactic radiosurgery (e.g., gamma knife, linear-accelerated-based radiosurgery, charged particles, and CyberKnife). Multiple local (brain) therapies or combinations of local therapies are allowed. For patients receiving local therapy to all brain lesions (including WBRT), progression of pre-existing lesions based on RECIST 1.1 (> 20% increase in longest diameter on baseline scan) or new measurable lesions are required. For patients receiving local therapy for some but not all lesions, disease progression based on RECIST 1.1 is not required as long as there are remaining brain lesions that are measurable and not previously treated.

Phase 2 Arm A Cohort 2:

• Received no prior local therapy (e.g., brain surgery, craniotomy, SRS or SRT) for brain metastases;
• All patients (Safety Lead-In and Phase 2): May have received prior immunotherapy;
• All patients (Safety Lead-In and Phase 2): If receiving concomitant corticosteroids must be on a stable or decreasing dose (up to a total daily dose of 4 mg of dexamethasone or equivalent) for at least 2 weeks prior to first dose of study treatment.
• An ECOG PS of 0 or 1 and Karnofsky score ≥ 80 (see Section 7.2.5).
• Adequate bone marrow, organ function and laboratory parameters:
  • ANC ≥ 1.5 × 10^9 /L;
  • Hemoglobin ≥ 9 g/dL with or without transfusions;
  • Platelets ≥ 100 × 10^9 /L;
  • AST and ALT ≤ 2.5 × ULN; in patients with liver metastases ≤ 5 × ULN;
  • Total bilirubin ≤ 1.5 × ULN.
    • Note: Patients with documented Gilbert syndrome or hyperbilirubinemia due to non-hepatic cause (e.g., hemolysis, hematoma) may be enrolled following discussion and agreement with the Sponsor Medical Monitor.
    • Serum creatinine ≤ 1.5 × ULN; OR calculated creatinine clearance > 50 mL/min by Cockcroft-Gault formula; OR estimated glomerular filtration rate > 50 mL/min/1.73m^2.
• Female patients of childbearing potential must have a negative serum β-HCG test result.
• Female patients of childbearing potential must agree to protocol-approved methods of contraception and to not donate ova from Screening until 30 days after the last dose of study drug.
• Male patients must agree to use methods of contraception that are highly effective or acceptable and to not donate sperm from Screening until 90 days after the last dose of study drug.
• The patient is deemed by the Investigator to have the initiative and means to comply with scheduled visits, treatment plan and study procedures.

Exclusion Criteria:

• ​​​​​​​Patients with symptomatic brain metastasis (e.g., have neurologic symptoms related to brain metastases).
• Prophylactic or preventive anti-epileptic therapy.
  • Note: Anti-epileptic therapy indicated in order to prevent neurologic symptoms caused by a preexisting condition and not related to brain metastasis is allowed.
• Known hypersensitivity or contraindication to any component of study treatment or their excipients.
• Inability to swallow and retain study treatment.
• Uveal or mucosal melanoma.
• History of or current leptomeningeal metastases.
• Treatment with SRS or craniotomy within 14 days prior to start of study treatment, or treatment with whole-brain radiation within 28 days prior to study treatment. Patients who received local therapy should have complete recovery with no neurological sequelae.
• Either of the following:
  • Radiation therapy to non-brain visceral metastasis within 2 weeks prior to start of study treatment;
  • Continuous or intermittent small-molecule therapeutics or investigational agents within 5 half-lives of the agent (or within 4 weeks prior to start of study treatment, when half-life is unknown).
• Patients treated in the adjuvant setting with BRAF or MEK inhibitor(s) < 6 months prior to enrollment. Patients who received BRAF or MEK inhibitors in the metastatic setting are excluded.
• Is currently participating in a study and receiving an investigational agent; has received an investigational agent or used an investigational device within 14 days prior to start of study treatment.
• Patients who have undergone major surgery (e.g., inpatient procedure with regional or general anesthesia) ≤ 6 weeks prior to start of study treatment. For minor surgical procedures ≤ 6 weeks prior to start of study treatment, consult the Sponsor Medical Monitor.
• Patient has not recovered to ≤ Grade 1 from toxic effects of prior therapy before starting study treatment. Note: Stable chronic conditions (≤ Grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and patients with these may enroll.
• Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6 months prior to Screening;
  • Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2);
  • An LVEF < 50% as determined by MUGA or ECHO; d. Uncontrolled hypertension defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy;
  • History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia); f. Triplicate average baseline QTcF interval ≥ 480 msec.
• Continuous or intermittent small-molecule therapeutics or investigational agents within 5 half-lives of the agent (or within 4 weeks prior to start of study treatment, when half-life is unknown). 9. Patients treated in the adjuvant setting with BRAF or MEK inhibitor(s) < 6 months prior to enrollment. Patients who received BRAF or MEK inhibitors in the metastatic setting are excluded.
• Is currently participating in a study and receiving an investigational agent; has received an investigational agent or used an investigational device within 14 days prior to start of study treatment.
• Patients who have undergone major surgery (e.g., inpatient procedure with regional or general anesthesia) ≤ 6 weeks prior to start of study treatment. For minor surgical procedures ≤ 6 weeks prior to start of study treatment, consult the Sponsor Medical Monitor.
• Patient has not recovered to ≤ Grade 1 from toxic effects of prior therapy before starting study treatment. Note: Stable chronic conditions (≤ Grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and patients with these may enroll.
• Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6 months prior to Screening;
  • Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2);
  • An LVEF < 50% as determined by MUGA or ECHO;
  • Uncontrolled hypertension defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy;
  • History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
  • Triplicate average baseline QTcF interval ≥ 480 msec.
• Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study.