Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma

Inclusion Criteria

• Key Inclusion Criteria: Patients must meet all of the following criteria to be eligible for enrollment in the study. - Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer Stage IIIB, IIIC, or IV. - Presence of BRAF V600E or V600K mutation in tumor tissue as determined by a local or central laboratory - Adequate cardiac function: - Left ventricular ejection fraction (LVEF) ≥ 50% as determined by ECHO or multi-gated acquisition (MUGA) scan and above the institutional lower limit of normal (LLN); - Triplicate average baseline QTcF value ≤ 450 ms. - Adequate bone marrow, organ function, and laboratory parameters: - Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; - Hemoglobin ≥ 9 g/dL with or without transfusions; - Platelets ≥ 75 × 10⁹/L without transfusions; - Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); in patients with liver metastases ≤ 5 × ULN; - Total bilirubin ≤ 1.5 × ULN; - Creatinine ≤ 1.5 × institutional ULN for age, or calculated creatinine clearance ≥ 70 mL/min/1.73 m² (following Schwartz formula). - Adequate performance status at Screening: - Patients < 16 years old: Lansky Performance Scale score ≥ 80 - Patients 16 to 17 years old: Karnofsky Performance Scale score ≥ 80 Key Exclusion Criteria: Patients meeting any of the following criteria are not eligible for enrollment in the study. - Uveal or mucosal melanoma. - Brain metastases that are uncontrolled or symptomatic, require steroids, are potentially life-threatening or have required radiation within 28 days prior to starting study drug. - History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO - Prior therapy with a BRAF inhibitor (e.g., dabrafenib, vemurafenib) and/or a MEK inhibitor (e.g., trametinib, cobimetinib). - Impaired cardiovascular function or clinically significant cardiovascular disease, including any of 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, - Symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia. - Concurrent neuromuscular disorder associated with elevated creatine kinase (CK) - Uncontrolled arterial hypertension despite medical treatment - Presence of BRAFʷͭ or indeterminate melanoma in tumor tissue.