A Phase I Open-label, Multicenter Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of PLB1001 in Patients With Met-positive (Met+) Advanced Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Percentage of participants with dose-limiting toxicities
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 PLB1001.
详细描述
This is a Phase I, open-label, multicentre study of PB1001 administered orally to patients with Met-positive (Met+) 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 PLB1001 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 PLB1001 single agent. Aprox. 40 patients will be enrolled in PART A, while 20-30 patients for expansion cohort .
PLB1001 is a potent selective c-Met inhibitor. PLB1001 acts on cancer by blocking abnormal cmet-mediated signalling, leading to profound tumour growth inhibition in xenografts of non-small cell lung cancer (NSCLC) tumours. Preliminary data from a c-Met inhibitor INC 280 has provided possibility on the safety and clinical activity of PLB1001 monotherapy in this patient population.
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
- •Histologically or cytologically confirmed advanced non-small cell lung cancer
- •Must have evidence of c-Met 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
- •Previous or current treatment with a c-Met inhibitor or HGF-targeting therapy
- •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 > II) Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 140 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 90 mm Hg Arrhythmias
- •Active peptic ulcer disease or gastritis
- •Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1, except for alopecia
- •Major surgery within 4 weeks prior to starting PLB1001
- •Previous anti-cancer and investigational agents within 4 weeks before first dose of PLB
- •If previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 6 weeks before first dose of PLB
- •Pregnant or nursing women
- •Involved in other clinical trials < 30 days prior to Day 1
研究组 & 干预措施
PLB1001
There are 5 dose cohorts, including 50mg BID, 100mg BID, 150mg BID, 200mg BID and 275mg BID in the dose escalation stage and PLB1001 will be administered orally to patients twice daily for each dose cohort.
干预措施: PLB1001 (Drug)
结局指标
主要结局
Percentage of participants with dose-limiting toxicities
时间窗: 2 years
次要结局
- Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite(Day 1-2 Single Dose and Day 1-28 Steady State)
- Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite(Day 1-2 Single Dose and Day 1-28 Steady State)
- Time to Cmax (Tmax) of PLB1001 and its metabolite(Day 1-2 Single Dose and Day 1-28 Steady State)
- Preliminary antitumor activity of PLB1001(2 years)