A Phase I Open-label, Multicenter Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of PLB1003 in Patients With ALK-positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs) .
研究概览
简要总结
This phase I, first-in-human dose-escalation study was conducted to determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), dose-limiting toxicities (DLTs), pharmacokinetics (PK) profile, and preliminary antitumor activity of PLB1003.
详细描述
This is a Phase I, open-label study of PB1003 administered orally to patients with ALK-positive (ALK+) advanced NSCLC. The study includes a Dose-escalation Part (part A) and a Dose Expansion Part (part B). The aim of the part A is to estimate the MTD and to identify the dose limited toxicity(DLT) and the recommended phase II dose (RP2D) for PLB1003 single agent as well as to determine the PK/PD profile. Once response has been observed in certain dose level, then followed by the expansion part to further assess the clinical efficacy and safety of PLB1003 single agent. Aprox 40 patients will be enrolled in PART A, while 12-24 patients for expansion cohort .
PLB1003 is a potent selective ALK inhibitor. PLB1003 acts on cancer by blocking abnormal ALK-mediated signaling, leading to profound tumour growth inhibition in xenografts of non-small cell lung cancer (NSCLC) tumours.
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
- •Signed Informed Consent Form
- •Age≥18 years
- •Diagnosed with a locally advanced or metastatic non-small cell lung cancer that has progressed despite standard therapy.
- •Must have evidence of ALK positivity from the results of molecular pre-screening evaluations
- •At least one measurable lesion as per RECIST v1.1
- •Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1
- •ECOG Performance Status of 0-2
排除标准
- •Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring increasing doses of steroids to control, and patients with any CNS deficits.
- •Clinically significant, uncontrolled heart diseases. Unstable angina. History of documented congestive heart failure (New York Heart Association functional classification III-IV) .
- •Active peptic ulcer disease or gastritis
- •Major surgery within 4 weeks prior to starting PLB1003
- •Previous anti-cancer and investigational agents within 4 weeks before first dose of PLB1003..
- •Pregnant or nursing women
- •Involved in other clinical trials < 30 days prior to Day 1
研究组 & 干预措施
PLB1003
ALK-positive (ALK+) advanced NSCLC
干预措施: PLB1003 (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs) .
时间窗: 18 months.
The maximum tolerated dose (MTD) was defined as the highest dose for a given schedule that was expected to cause DLTs in no more than 33% of patients during the first cycle of treatment.
次要结局
- Area under the plasma concentration versus time curve (AUC) of PLB1003 and its metabolite.(Day 1-3 PK Run-in period and Day 1-21 Treatment period)
- Maximum plasma concentration observed (Cmax) of PLB1003 and its metabolite.(Day 1-3 PK Run-in period and Day 1-21 Treatment period)
- Time to Cmax (Tmax) of PLB1003 and its metabolite.(Day 1-3 PK Run-in period and Day 1-21 Treatment period)
- Preliminary antitumor activity of PLB1003.(30 months.)