Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 9
- 主要终点
- Determination of Recommended Phase 2 Dose (RP2D) of BVD-523 by Dose-limiting Toxicities (DLT).
研究概览
简要总结
This open-label, multi-center Phase 1/2 study will assess the safety, pharmacokinetics, and pharmacodynamics of escalating doses of BVD-523 in patients with advanced malignancies. The study also seeks to demonstrate target modulation and early signs of clinical response in select patient populations.
详细描述
The study is being performed to assess the safety and tolerability of BVD-523
In Part 1 of the study, an accelerated dose escalation plan will be used to establish dose limiting toxicities, maximum tolerated dose, and the recommended Phase 2 dose.
In Part 2 of the study, additional patients with particular tumor types and/or cancers harboring specific genetic mutations will be recruited for treatment at the Recommended Phase 2 Dose. Patients may also be assessed pharmacodynamic measures in healthy or malignant tissues, using biomarker assays for phosphorylation, cytotoxic or cytostatic measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with metastatic or advanced-stage malignant tumor. Patients may have received up to 2 prior lines of chemotherapy for their metastatic disease
- •ECOG score of 0 or 1
- •Predicted life expectancy of ≥ 3 months
- •Adequate bone marrow, liver and renal function renal function
- •Adequate cardiac function
- •For women: Negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal, or compliant with a contraceptive regimen during and for 3 months after the treatment period
- •For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 3 months after the treatment period
- •For Part 2 of the Study only, patients must have measurable disease by RECIST 1.1 and be in one of the the groups below. Patients in groups 1, 2, 4, 5 and 6 may not have been previously treated with BRAF and/or MEK inhibitors
- •Group 1: Patients with BRAF mutated cancer, except those with colorectal or non-small cell lung cancers
- •Group 2: Patients with BRAF mutated colorectal cancer
- •Group 3: Patients with BRAF mutated melanoma who have progressed on, or are refractory to BRAF and/or MEK inhibitors
- •Group 4: Patients with NRAS mutated melanoma
- •Group 5: Patients with MEK mutated cancer
- •Group 6: Patients with BRAF mutated non-small cell lung cancer
- •Group 7: Patients with ERK mutated cancer
排除标准
- •Gastrointestinal condition which could impair absorption of study medication
- •Uncontrolled or severe intercurrent medical condition
- •Known uncontrolled brain metastases. Stable brain metastases either treated or being treated with a stable dose of steroids/anticonvulsants
- •Any cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc.) within 28 days or 5 half-lives, whichever is shorter
- •Major surgery within 4 weeks prior to first dose
- •Any use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of BVD-
- •Pregnant or breast-feeding women
- •Any evidence of serious active infections
- •Any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study
- •A history or current evidence/risk of retinal vein occlusion or central serous retinopathy
- •Concurrent therapy with any other investigational agent
- •Concomitant malignancies or previous malignancies with less than 2 years disease-free interval at the time of enrollment
研究组 & 干预措施
BVD-523
干预措施: BVD-523 (Drug)
结局指标
主要结局
Determination of Recommended Phase 2 Dose (RP2D) of BVD-523 by Dose-limiting Toxicities (DLT).
时间窗: As indicated by safety and tolerability during study conduct; ~42 months
DLT is defined as any BVD-523 related toxicity in the first 21 days of treatment that results in: 1. ≥Grade 4 hematologic toxicity for \>1 day; 2. Grade 3 hematologic toxicity with complications e.g., thrombocytopenia with bleeding; 3. ≥Grade 3 non-hematologic toxicity, except untreated nausea, vomiting, constipation, pain and rash (these become DLTs if the adverse event (AE) persists despite adequate treatment), a doubling of aspartate transaminase (AST)/alanine transaminase (ALT) in patients with grade 2 ALT/AST at baseline; 4. A treatment interruption exceeding 5 days (or an interruption exceeding 7 days for rash, despite adequate treatment) in Cycle 1 (or inability to begin Cycle 2 for \> 7 days) due to BVD-523-related toxicity.
次要结局
- Clinical Evidence of Tumor Response Assessed by Physical or Radiological Exam.(Patients will be evaluated at baseline & at periodic follow-up visits through the time their participation in the study is completion. The best responses presented occurred at different time points for each patient.)
- Characterization of the Time Versus Plasma Concentration Profiles of BVD-523 and Selected Metabolites.(Samples will be collected on day 1 and day 15 of Cycle 1)