A Phase Ib/II, Open-Label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ABT-101 in Patients With Advanced Solid Tumors and HER2 Exon 20 Insertions Mutated Non- Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 61
- 试验地点
- 5
- 主要终点
- Determine the recommended Phase 2 Dose (RP2D) of ABT-101 in Part 1
研究概览
简要总结
A Phase 1b/2, open-label, multicenter study to determine the recommended phase 2 (RP2D) of ABT-101in solid tumor and to explore antitumor activities of ABT-101 in patients with HER 2 mutated non-small cell lung cancer (NSCLC)
详细描述
This study will be conducted in two parts:
Part 1: Dose- Escalation, Phase 1b, is designed to determine the RP2D. Patients with solid tumor will be enrolled into a dose finding study scheme with the assessment of dose-limiting toxicities (DLTs). DLT assessment will be conducted during treatment cycle 1
Part 2: Dose- Expansion, Phase 2, will evaluate the safety and efficacy of ABT-101 at the dosage and dosing regime determined in Phase 1b. Phase 2 will enroll NSCLC patients with HER2 mutations
Study participation for all patients includes screening period, treatment period and safety/ follow-up period. Patient will received study treatment until progressive disease or any other discontinuation or withdrawal criterion is met
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
- •Male or female aged ≥ 20 years or adult age as per local regulations, at time of informed consent
- •Histologically or cytologically confirmed advanced solid tumor (Part 1) or NSCLC with HER2 mutations as determined by the central result (Part 2)
- •For patients in Part 2 only: Patients has measurable disease per RECIST 1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Part 1), 0 to 2 (Part 2)
- •Appropriate candidate for experimental therapy
- •Adequate organ function
排除标准
- •Known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
- •For patients in Part 2 only: Previously treated with EGFR or HER2 TKIs.
- •Serious acute or chronic infections
- •Received a live-virus vaccination
- •Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose.
- •Not recovered from prior- treatment toxicities to Grade ≤1
- •Major surgery within 28 days prior to the study treatment
- •Concurrent malignancy within 2 years prior to first dose
- •History or presence of clinically relevant cardiovascular abnormalities. QTcF ≥ 470 ms
- •Significant gastrointestinal disorder(s) that could interfere with absorption of ABT101
- •Known to have a history of alcoholism or drug abuse
研究组 & 干预措施
ABT-101
Part 1- dose-escalation: ABT-101 in patients with advanced cancer disease
Part 2- dose expansion: ABT-101 in patients with NSCLC with confirmed HER2 mutations
干预措施: ABT-101 (Drug)
结局指标
主要结局
Determine the recommended Phase 2 Dose (RP2D) of ABT-101 in Part 1
时间窗: 18 months
Determine the maximum tolerated dose (MTD) and RP2D of ABT-101 based on Dose Limiting Toxicities
Determine antitumor activity based on Objective Response Rate (ORR) in Part 2 in patients with NSCLC with targeted mutation
时间窗: 36 months
Patients response according to RECIST 1.1
次要结局
- Duration of response (DOR)(48 months)
- Progression- free survival (PFS)(36 months)
- Maximum plasma concentration (Cmax) ABT-101(48 months)
- Overall survival (OS)(36 months)
- Area under the plasma concentration time curve (AUC) of ABT-101(48 months)
- Objective response rate (ORR) in Part 1(12 months)
- Disease control rate (DCR)(36 months)