A Study of a Selective ERBB2 Inhibitor, CGT4255, in Patients With Advanced Solid Tumors With ERBB2 Genetic Alterations or HER2 Overexpression
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 15
- 主要终点
- Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part A]
研究概览
简要总结
This is an open-label, phase 1/1b study evaluating the safety, tolerability, pharmacokinetic (what the body does to the drug), pharmacodynamic (what the drug does to the body), and antitumor activity of CGT4255 in adult participants with advanced solid tumors with ERBB2 alterations or HER2 overexpression.
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
- •Have histologically confirmed diagnosis of:
- •Part A: Locally advanced, metastatic, and/or unresectable solid tumor with documented ERBB2-activating alteration or NRG1 gene fusion in blood and/or tumor or HER2 overexpression in tumor
- •Part B: Locally advanced, metastatic, and/or unresectable NSCLC with documented ERBB2 mutation in blood and/or tumor
- •Part C: Locally advanced, metastatic and/or unresectable breast cancer with documented ERBB2 mutation in blood and/or tumor or HER overexpression in tumor
- •Have measurable disease per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 for Part A. For Parts B and C, ECOG Performance Status must be 0 to
- •Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits.
排除标准
- •Received small molecule chemotherapy or anticancer therapies or radiotherapy within certain timeframes before first dose of study drug.
- •Major surgeries (eg, craniotomy and thoracotomy) within 4 weeks of the first dose of study drug.
- •Treatment with palliative focal radiotherapy (cranial or extracranial) (eg, stereotactic radiosurgery or intensity-modulated radiation therapy) ≤2 weeks before the first dose of study drug; treatment with whole-brain radiotherapy ≤4 weeks before the first dose of study drug.
- •Clinically significant cardiac disease.
- •Resolution of toxicities from prior therapy to ≤Grade 1 (or baseline), including resolution of clinically significant laboratory abnormalities, before the first dose of study drug.
- •Restrictions on use of corticosteroid use to manage neurologic symptoms in different parts of the study.
研究组 & 干预措施
Signal Seeking and Dose Escalation
Part B: Signal Seeking and Dose Optimization Oral dose(s) of CGT4255 at the selected dose levels determined in Phase 1
干预措施: CGT4255 (Drug)
Dose Escalation
Part A: Dose Escalation Multiple doses of CGT4255 for oral administration
干预措施: CGT4255 (Drug)
Signal Seeking
Part C: Includes signal seeking. Participants will receive CGT4255 at a dose level selected based on data from Part A
干预措施: CGT4255 (Drug)
结局指标
主要结局
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part A]
时间窗: Approximately 12 months
1\. Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) and AEs leading to dose modifications and dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) or the maximum evaluated dose (MED) in participants with ERBB2-altered advanced solid tumors
Overall Response Rate [Part B and Part C]
时间窗: Approximately 6 months
Overall Response Rate (ORR), determined by confirmed CR + PR of all lesions (intracranial and extracranial), based on Investigator assessment using the whole-body RECIST v1.1 in participants with ERBB2-mutated NSCLC with Brain Metastases (BM) and in participants with ERBB2-mutated or HER2-positive breast cancer with BM ± leptomeningeal disease (LMD)
次要结局
- Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part B and C](Approximately 7 months)
- Pharmacokinetics [Part A](Approximately 28 days)
- Pharmacokinetics [Part A)(Approximately 28 days)
- Disease Response [Part A](Approximately 6 months)
- Disease Response [Part B and Part C](Approximately 6 months)