A Multicenter, Open-label Phase 1b Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600-mutant Melanoma

Pfizer1 个研究点分布在 1 个国家目标入组 1 人开始时间: 2020年8月3日最近更新: 2023年4月3日

适应症

干预措施

试验速览

阶段: 1 期
状态: 终止
发起方: Pfizer
入组人数: 1
试验地点: 1
主要终点: PK parameter (Cmax) for LHY746

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 12 Years 至 17 Years（Child）
性别: All
接受健康志愿者: 否

入选标准

•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

排除标准

•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.

研究组 & 干预措施

Safety Run-in Phase

Experimental

binimetinib taken twice daily (BID) and
encorafenib taken once daily (QD)

Dose levels by patient body surface area (BSA) for binimetinib and encorafenib tablets/capsules are specified in the protocol.

干预措施: binimetinib (Drug)

Safety Run-in Phase

Experimental

binimetinib taken twice daily (BID) and
encorafenib taken once daily (QD)

Dose levels by patient body surface area (BSA) for binimetinib and encorafenib tablets/capsules are specified in the protocol.

干预措施: encorafenib (Drug)

Expansion Phase

Experimental

binimetinib taken twice daily (BID) and
encorafenib taken once daily (QD)

Dose levels by patient body surface area (BSA) for binimetinib and encorafenib tablets/capsules and pediatric formulations are specified in the protocol.

干预措施: binimetinib (Drug)

Expansion Phase

Experimental

binimetinib taken twice daily (BID) and
encorafenib taken once daily (QD)

Dose levels by patient body surface area (BSA) for binimetinib and encorafenib tablets/capsules and pediatric formulations are specified in the protocol.

干预措施: encorafenib (Drug)