A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of Second Mitochondrial-derived Activator of Caspases Mimetic BGB-24714 as Monotherapy and With Combination Therapies in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 157
- 试验地点
- 68
- 主要终点
- Dose Escalation: Maximum tolerated dose (MTD) of BGB-24714 as monotherapy, in combination with chemotherapy, and in combination with concurrent chemoradiotherapy (cCRT)
研究概览
简要总结
This study aims to understand how safe and well-tolerated a drug called BGB-24714 is when used alone, or in combination with chemotherapy or radiation therapy, for people with advanced or spreading solid tumors. The main objective is to identify the highest tolerable dose or the highest administered dose of BGB-24714. Additionally, the study aims to identify the most suitable doses for further investigation in larger groups of participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Key Eligibility Criteria :
- •Participants must sign a written informed consent form (ICF); and agree to comply with study requirement
- •Phase 1a (Dose Escalation):
- •Part A, A-CN, and B: Participants with histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumor previously treated with standard systemic therapy or for whom treatment is not available or not tolerated Note: Only Chinese participants will be eligible for Part A-CN.
- •Part C: Participant has histologically or cytologically confirmed, locally advanced, unresectable Stage III Non-small cell lung cancer (NSCLC) suitable for definitive chemoradiotherapy (CRT)
- •Part D: Participant with locally advanced, histologically confirmed inoperable esophageal squamous cell carcinoma (ESCC) suitable for definitive CRT
- •Phase 1b (Dose Expansion): Participants with histologically or cytologically confirmed solid tumors of selected types previously treated with standard therapy.
- •Participants must be able to provide formalin-fixed paraffin embedded (FFPE) tumor tissue sample.
- •Phase 1a Part A, A-CN, B and Phase 1b: ≥ 1 measurable lesion per Response evaluation criteria in solid tumors (RECIST) v1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
排除标准
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- •Any malignancy ≤ 3 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent
- •Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s).
- •Clinically significant infection requiring systemic therapy ≤ 14 days before the first dose of study drug(s).
- •Prior exposure to agents with second mitochondria-derived activator of caspases (SMAC) mimetics, or other Inhibitors of apoptosis proteins (IAPs) antagonists.
- •NOTE: Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Phase 1a: Dose Escalation Part C
Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation
干预措施: Paclitaxel (Drug)
Phase 1a: Dose Escalation Part C
Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation
干预措施: Carboplatin (Drug)
Phase 1a: Dose Escalation Part C
Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation
干预措施: BGB-24714 (Drug)
Phase 1a: Dose Escalation Part A
Participants will receive escalating doses of BGB-24714 as monotherapy
干预措施: BGB-24714 (Drug)
Phase 1a: Dose Escalation Part B
Participants will receive increasing dose levels of BGB-24714 in combination with paclitaxel
干预措施: BGB-24714 (Drug)
Phase 1a: Dose Escalation Part B
Participants will receive increasing dose levels of BGB-24714 in combination with paclitaxel
干预措施: Paclitaxel (Drug)
Phase 1a: Dose Escalation Part D
Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation
干预措施: BGB-24714 (Drug)
Phase 1a: Dose Escalation Part D
Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation
干预措施: Paclitaxel (Drug)
Phase 1a: Dose Escalation Part D
Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation
干预措施: Carboplatin (Drug)
Phase 1a: Dose Escalation Part A-CN
Participants will receive escalating doses of BGB-24714 as monotherapy in Chinese participants
干预措施: BGB-24714 (Drug)
Phase 1a: Dose Escalation Part E
Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation in Chinese participants
干预措施: BGB-24714 (Drug)
Phase 1a: Dose Escalation Part E
Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation in Chinese participants
干预措施: Paclitaxel (Drug)
Phase 1a: Dose Escalation Part E
Participants will receive increasing dose levels of BGB-24714 in combination with chemoradiation in Chinese participants
干预措施: Carboplatin (Drug)
Phase 1b: Dose Expansion
BGB 24714 will be administered in combination with paclitaxel or docetaxel in participants with selected solid tumors.
干预措施: BGB-24714 (Drug)
Phase 1b: Dose Expansion
BGB 24714 will be administered in combination with paclitaxel or docetaxel in participants with selected solid tumors.
干预措施: Paclitaxel (Drug)
Phase 1b: Dose Expansion
BGB 24714 will be administered in combination with paclitaxel or docetaxel in participants with selected solid tumors.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Dose Escalation: Maximum tolerated dose (MTD) of BGB-24714 as monotherapy, in combination with chemotherapy, and in combination with concurrent chemoradiotherapy (cCRT)
时间窗: approximately 6 months
Dose Escalation: Recommended Doses for Expansion (RDFE) of BGB-24714 as monotherapy, in combination with chemotherapy, and in combination with concurrent chemoradiotherapy (cCRT)
时间窗: approximately 6 months
Recommended dose based upon the MTD or MAD, as well as the long-term tolerability, pharmacokinetics, efficacy, and any other relevant data as available
Dose Expansion: Objective response rate (ORR)
时间窗: approximately 2 Years
ORR is defined as the percentage of participants with partial or complete response, as determined by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Dose Escalation: Number of participants with adverse events (AEs)
时间窗: approximately 6 months
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs ), and experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria.
次要结局
- Dose Escalation: Objective response rate (ORR)(approximately 2 Years)
- Duration of Response (DOR)(approximately 2 Years)
- Time to Maximum Plasma Concentration (Tmax) of BGB-24714 and its metabolite(Up to 48 hours postdose)
- Concentration at steady state (Cmax,ss) of BGB-24714 and its metabolite(Up to 48 hours postdose)
- Dose Expansion: Number of participants with adverse events(approximately 2 Years)
- Disease Control Rate (DCR)(approximately 2 Years)
- Area Under the Plasma Concentration Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of BGB-24714 and its metabolite(Up to 48 hours postdose)
- Area Under The Plasma Concentration Time Curve From Time 0 To Infinity (AUC0-inf) of BGB-24714 and its metabolite(Up to 48 hours postdose)
- Rough Concentration At Steady State (Ctrough,ss) of BGB-24714 and its metabolite(Up to 48 hours postdose)
- Plasma Concentrations of BGB-24714 and its metabolite(approximately 2 Years)
- Clinical Benefit Rate (CBR)(approximately 2 Years)
- Maximum Observed Plasma Concentration (Cmax) of BGB-24714 and its metabolite(Up to 48 hours postdose)
- Apparent Clearance (CL/F) of BGB-24714(Up to 48 hours postdose)
- Apparent Volume Of Distribution (Vz/F) of BGB-24714(Up to 48 hours postdose)
- Dose Expansion: Progression-free Survival (PFS)(approximately 2 Years)
- Terminal Half-life (t1/2) of BGB-24714 and its metabolite(Up to 48 hours postdose)
- Time to Maximum Plasma Concentration at steady state (Tmax,ss) of BGB-24714 and its metabolite(Up to 48 hours postdose)
- Area Under the Plasma Concentration Time Curve from Time 0 to the Last Quantifiable Concentration at Steady State (AUClast,ss) of BGB-24714 and its metabolite(Up to 48 hours postdose)