A Phase I, Open-Label, Multi-Center Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of ATG-017 Monotherapy or Combination Therapy With Nivolumab in Patients With Advanced Solid Tumors and Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 36
- 试验地点
- 5
- 主要终点
- AEs/SAEs
研究概览
简要总结
This is a Phase I, multi-center, open-label study of ATG-017 administered orally, alone or in combination with nivolumab in patients with advanced solid tumors and hematological malignancies. The study is composed of two modules: ATG-017 monotherapy (Module A) and ATG-017 in combination with nivolumab (Module B). Both Modules A and B will include Dose Escalation Phase and Dose Expansion Phase.
详细描述
The dose escalation of ATG 017 will be conducted with intensive safety monitoring to ensure the safety of the patients with solid tumors (Module A and Module B) and hematological malignancies (Module A) harbouring activating alterations in the RAS-MAPK pathway, and will include the continuous and intermittent dosing schedules.
The Dose Expansion Phase will start based on dose level and schedule (continuous or intermittent)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
- •Aged at least 18 years.
- •Module A: Patient must have a documented activating alteration of the RAS-MAPK pathway.
- •Module B: Dose Escalation Phase: Patient must have a documented activating alteration of the RAS-MAPK pathway; Dose Expansion Phase: Expansion cohorts will be further defined based on information from the Dose Escalation.
- •Histological or cytological confirmation of a solid tumour.
- •Patient with solid tumors must have at least 1 lesion, not previously irradiated.
- •Estimated life expectancy of minimum of 12 weeks.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Ability to swallow and retain oral medication.
排除标准
- •Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.
- •Prior ATG-017 administration in the present study.
- •Prior treatment with an ERK1/2 inhibitor.
- •Prior major surgery within 28 days of the first dose of study treatment or minor surgical procedures ≤7 days.
- •Patients receiving unstable or increasing doses of corticosteroids.
- •As judged by the investigator, any evidence of severe or uncontrolled systemic diseases.
- •Active infection including hepatitis B, and/or hepatitis C.
- •Known history of human immunodeficiency virus (HIV) infection.
- •Inadequate bone marrow reserve or organ function
研究组 & 干预措施
Module A (ATG-017 Monotherapy)
Dosing will begin at 5 mg QD ATG-017 as starting dose. A treatment cycle will be 21 days for continuous dosing and 28 days for 7 days on/7 days off intermittent dosing of ATG-017 treatment.
干预措施: ATG-017 (Drug)
Module B (ATG-017+Nivolumab Combination Therapy in Solid Tumors)
With the combination with nivolumab, a cycle of study treatment will be defined as 28 days. ATG-017 is planned initially to be continuously given 28 days in each cycle. ATG-017 dosing schedule in combination therapy will follow a similar dose escalation principle as with monotherapy but starting at 5 mg BID. Nivolumab will be given at fixed dosing, 480 mg Q4W, on D1 of each cycle.
干预措施: ATG-017+Nivolumab (Drug)
结局指标
主要结局
AEs/SAEs
时间窗: 18 months
Toxicity will be graded according to the NCI CTCAE, Version 5.0.
次要结局
- Plasma concentrations(18 months)
- Overall Response Rate (ORR)(18 months)
- DOR(18 months)
- Progression-Free Survival (PFS)(18 months)