A Phase 1/2, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of JIN-A02 in Patients With EGFR Mutant Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- J Ints Bio
- 入组人数
- 150
- 试验地点
- 10
- 主要终点
- Adverse Events (AE) rate
研究概览
简要总结
This study is a Phase I/II open-label, multi-center study to evaluate the safety, tolerability, PK, and an anti-tumor activity of JIN-A02, a 4th generation EGFR-TKI agent for oral administration, in EGFR mutant-positive, advanced NSCLC subjects who showed disease progression after receiving standard anticancer therapy, including approved EGFR-TKI therapy and/or no more than a single platinum-based anticancer chemotherapy. In Part A of the study, dose escalation is carried out where MTD is evaluated using Bayesian Optimal Interval (BOIN) design in subjects with advanced NSCLC harboring EGFR-mutation of C797S or T790M. In Part B, dose exploration is carried out to further evaluate the safety of JIN-A02 and to determine the RP2D using 2 preliminary effective dose levels and with the help of a safety review committee (SRC) in advanced NSCLC subjects harboring EGFR mutant C797S or T790M. In Part C dose expansion study, subjects with EGFR mutant who show disease progression after receiving standard anticancer therapy, including approved EGFR-TKI therapy with activity against T790M such as Osimertinib and/or no more than one platinum-based anticancer chemotherapy, are divided into 5 different cohorts based on the EGFR mutation and the anti-tumor activity of JIN-A02 is evaluated. Before enrollment in the study, the EGFR mutant profile is determined using either tumor tissue and/or plasma ctDNA. The profile is determined locally through a test method approved by the sponsor. The sponsor reviews and approves each potential subject for enrollment. Study eligibility evaluation will utilize local test(s).
详细描述
<Part A: Dose Escalation Study> This part of the study evaluates MTD using the BOIN design in advanced or metastatic NSCLC subjects with EGFR mutant C797S or T790M. The target DLT rate for determination of MTD in this study is 30%. The administration cycle is defined as 28 days and JIN-A02 is administered QD. The DLT period for each subject is 21 days. When a subject receives at least 75% of his or her assigned daily dose during the DLT period or shows DLT during the DLT period, the subject is considered evaluable for DLT.
The first cohort starts with 12.5 mg QD, and at least 3 subjects will be recruited per cohort. Dose escalation between cohorts is made at up to twice the prior dose level. At any dose level, if DLT occurs to 1 subject or if 2 subjects experience a grade 2 or higher AE considered related to JIN-A02 during the first Cycle after administration, subsequent dose escalation shall be made at no more than 50%.
Before proceeding with a subsequent cohort, the SRC will convene and conducts a review meeting at a time point when subject DLT evaluation is available and then determines a subsequent dose level. In the Part A dose escalation study, the estimated sample size is 30 subjects, and if an additional dose cohort is added, the maximum sample size can be increased by 6 subjects per dose level. If there is no DLT or disease progression in subjects after Cycle 1 (28 days), the dose level can be maintained or escalated as determined by the investigator though it must not exceed the MTD determined, or the level reviewed by SRC at that time. If there is a subject who withdraws from the study before completion of Cycle 1 due to reasons other than DLT, the subject can be replaced for MTD determination. The total number of subjects for a given dose level must not exceed 12. If 12 subjects are evaluable for DLT at a given dose level, it is considered that the dose escalation has been completed.
Additionally, if a dose level has not exceeded the level approved by SRC and a subject has completed administration for 8 weeks or longer without experiencing a grade 3/4 AE or DLT, dose escalation is permitted for these subjects who were enrolled to the earlier lower dose levels.
<Part B: Dose Exploration Study> This part of the study is to determine the optimal RP2D by further investigating safety, tolerability, PK and efficacy of JIN-A02. SRC will select 2 preliminary effective dose levels based on the results of Part A and additionally enrolls 3 to 6 subjects to each of the 2 dose levels. Up to 12 evaluable subjects are expected per dose level, including those previously enrolled in Part A of the study. If data for the 12 subjects have been collected at a dose level during the dose escalation phase, an exploratory cohort may not be required at the same dose level. SRC will determines the RP2D based on the dose escalation phase and dose exploration phase of this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase 1 dose-escalation, Phase 1 dose-exploratory, Phase 2 dose-expansion
Single arm
干预措施: JIN-A02 (Drug)
结局指标
主要结局
Adverse Events (AE) rate
时间窗: 28 days
Safety evaluation is analyzed based on the Safety Set. Safety is clinically evaluated by assessing all relevant endpoints, including AE, SAE, laboratory tests, vital signs, ECG results and concomitant drugs. Reported AE terminologies are standardized using MedDRA and the AE grade and intensity are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. The AE summary focuses on AE that first occurred after initial administration of IP or that occurred after administration as an aggravation of pre-existing symptoms. AEs are summarized by the number and percentage of subjects experiencing AE per cohort based on the System Organ Class (SOC) and Preferred Term (PT).
Serious Adverse Events (SAE) rate
时间窗: 28 days
Safety evaluation is analyzed based on the Safety Set. Safety is clinically evaluated by assessing all relevant endpoints, including AE, SAE, laboratory tests, vital signs, ECG results and concomitant drugs. Reported AE terminologies are standardized using MedDRA and the AE grade and intensity are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. The AE summary focuses on AE that first occurred after initial administration of IP or that occurred after administration as an aggravation of pre-existing symptoms. AEs are summarized by the number and percentage of subjects experiencing AE per cohort based on the System Organ Class (SOC) and Preferred Term (PT).
Maximum Tolerable Dose (MTD)
时间窗: 28 days
In the Part A dose escalation study, MTD is evaluated in DLT Set. When the study ends according to the BOIN design, the DLT rate per dose level is estimated as posterior probability based on the beta-binomial model and 95% CI is presented. The dose level at which the estimated DLT rate is closest to the target toxicity rate 0.3 is selected as MTD. If two or more dose levels are selected at a rate lower than 0.3, a higher one is selected as MTD. If two or more dose levels are selected at a rate higher than 0.3, a lower one is selected as MTD.
Dose Limiting Toxicity (DLT)
时间窗: 21 days
DLT is evaluated for all subjects enrolled to cycle 1 (DLT evaluation period: 21 days) of the Part A dose escalation study. When a subject receives at least 75% of his or her assigned daily dose during the DLT period or shows DLT, the subject is considered evaluable for DLT. All AEs that occur during the DLT period, are possibly related to JIN-A02 in the least and satisfy all of the following criteria are designated as DLT. Also, the occurrence of any of the toxicities outlined in this section will be considered a DLT unless clearly related to underlying disease or extraneous causes.
次要结局
未报告次要终点