A Phase 1/2, Dose Escalation and Expansion Study of TRI-611, an Oral ALK Molecular Glue Degrader in Participants With Advanced ALK-Positive NSCLC
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 160
- 试验地点
- 17
- 主要终点
- Part 1: Treatment emergent adverse events
研究概览
简要总结
The goal of this clinical trial is to learn about the safety and recommended dose of TRI-611 when administered to adults with ALK-positive non-small cell lung cancer (NSCLC). The trial will also evaluate the antitumor activity of TRI-611 in adults with ALK-positive NSCLC.
The study will be conducted in two parts. The first part will examine different doses of TRI-611. The second part will look at how well TRI-611 works on ALK-positive NSCLC when administered to three groups of participants that differ based on what type of prior therapy they have received.
In this study participants will:
- Take TRI-611 on a continued basis, provided it is well-tolerated, for as long as their disease is not progressing
- Visit the clinic approximately seven times in the first 3 months and then just once at the start of each 28-day cycle thereafter
- Keep a diary of each time they take the study medication
详细描述
This is a Phase 1/2 dose escalation and dose expansion study designed to evaluate the safety and tolerability of TRI-611, identify the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in participants with ALK-positive NSCLC.
Part 1 of the study consists of a dose escalation to determine the MTD and/or recommended dose(s) of TRI-611 for further exploration in two backfill cohorts.
Following completion of Part 1 of the study, Part 2 of the study will be initiated. The second part of the study is comprised of three cohorts (M1, M2, M3) of participants differentiated based on their previous treatment with ALK TKIs (tyrosine kinase inhibitors). During this part of the study the antitumor activity of TRI-611 will be further explored. See eligibility criteria for more details.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Pathologically confirmed diagnosis of ALK-positive non-small cell lung cancer (NSCLC)
- •Measurable disease per RECIST v1.1
- •Adequate bone marrow reserve and organ function
- •Part 1: prior treatment with 2 to 3 ALK TKIs [in US only: '2 or more ALK TKIs'], prior treatment with lorlatinib is required but must not have been in the first line
- •Part 2 Cohort M1: prior treatment with 2 to 3 ALK TKIs, prior treatment with lorlatinib is required but must not have been in the first line, prior treatment with neladalkib is excluded
- •Part 2 Cohort M2: prior treatment with more than 3 ALK TKIs, prior treatment with lorlatinib and neladalkib is required but neither may have been in the first line
- •Part 2 Cohort M3: participants without prior ALK TKI treatment
排除标准
- •Participant's cancer has any additional driver alterations known to be a mechanism of resistance to ALK TKIs
- •For participants with central nervous system (CNS) metastases or spinal cord compression, they must not be associated with progressive neurological symptoms or require increasing doses of corticosteroids to control the CNS disease
- •Ongoing treatment with another anticancer treatment or investigational agent
- •Known allergy/hypersensitivity to TRI-611 or any of its ingredients
- •Major surgery within 4 weeks of receiving the first dose of TRI-611
研究组 & 干预措施
Part 2: Cohort M3
Participants without prior ALK TKI treatment
干预措施: TRI-611 (Drug)
Part 2: Cohort M1
Prior treatment with ALK TKIs, including lorlatinib. Prior treatment with neladalkib is excluded
干预措施: TRI-611 (Drug)
Part 2: Cohort M2
Prior treatment with ALK TKIs, including lorlatinib. Prior treatment with neladalkib is required
干预措施: TRI-611 (Drug)
Part 1: Dose Escalation and Backfill
Prior treatment with 2 to 3 ALK TKIs, prior treatment with lorlatinib is required but must not have been in the first line
干预措施: TRI-611 (Drug)
结局指标
主要结局
Part 1: Treatment emergent adverse events
时间窗: Within 28 days of the first TRI-611 dose
Treatment emergent adverse events (TEAEs)
Part 2: Objective response rate (ORR)
时间窗: Approximately 16 weeks after the last participant dosed in Part 2
Determine the objective response rate (ORR) based on RECIST v1.1
Part 2: Depth of response (DofR)
时间窗: Approximately 16 weeks after the last participant dosed in Part 2
Defined as the greatest percentage reduction in the sum of diameters of target lesions from baseline
次要结局
- Part 1: Half-life (t1/2) of TRI-611(Pre-dose and up to 24 hours post-dose)
- Part 1: Area under the curve (AUC) of TRI-611(Pre-dose and up to 24 hours post-dose)
- Part 1: Maximum plasma concentration (Cmax) of TRI-611(Pre-dose and up to 24 hours post-dose)
- Part 1: Minimum plasma concentration (Cmin) of TRI-611(Pre-dose and up to 24 hours post-dose)
- Part 1: ORR(Approximately 16 weeks after the last participant dosed in Part 1)
- Part 1: DofR(Approximately 16 weeks after the last participant dosed in Part 1)
- Parts 1&2: Duration of response (DOR)(Approximately 5 years after the last participant is dosed with TRI-611)
- Parts 1&2: Disease control rate (DCR)(Approximately 16 weeks after the last participant dosed)
- Parts 1&2: Clinical Benefit Rate (CBR)(Approximately 9 months after the last participant is dosed)
- Parts 1&2: Progression-free survival (PFS)(Approximately 5 years after the last participant is dosed with TRI-611)
- Parts 1&2: Overall survival (OS)(Approximately 5 years after the last participant is dosed with TRI-611)
- Parts 1&2: Central Nervous System (CNS) objective response rate (ORR)(Approximately 16 weeks after the last participant dosed)
- Parts 1&2: CNS duration of response (DOR)(Approximately 5 years after the last participant is dosed with TRI-611)
- Parts 1&2: Time to intracranial progression (TTP)(Approximately 5 years after the last participant is dosed with TRI-611)
- Part 1: Profile changes in tumor ALK-fusion protein levels(Approximately 14 days after the last dose of participants in Part 1 that have consented to on-treatment biopsies)