study of the combination of binimetinib and encorafenib in adolescent patients with unresectable or metastatic braf v600-mutant melanoma

Conditions: Melanoma

Summary: this is a multicenter phase 1b, open-label study to evaluate the pharmacokinetic, safety and efficacy of binimetinib and encorafenib co-administered to adolescent patients with braf v600-mutant advanced/metastatic melanoma. the study consists of a safety run-in phase to determine the rde (recommended dose in expansion), followed by an expansion phase.

the study did not recruit the desired number of subjects and as a result does not have sufficient data for quantitative statistical analyses. additionally, results data cannot be reported because doing so would risk re-identification of the participant.

Eligibility 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.

Keywords: adolescent braf v600k braf v600e