NCT05205109招募中1 期
A Phase I/Ib, Multi-center, Open-label, and Dose-finding Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ATG-037 Monotherapy and Combination Therapy With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 98
- 试验地点
- 7
- 主要终点
- DLT
研究概览
简要总结
This is a study of ATG-037 Monotherapy and Combination Therapy with Pembrolizumab in Patients with Locally Advanced or Metastatic Solid Tumors
详细描述
This is a Phase I, Multi-center, Open-label, and Dose-finding Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ATG-037 Monotherapy and Combination Therapy with Pembrolizumab in Patients with Locally Advanced or Metastatic Solid Tumors.
Number of subjects :
- 39-51 subjects for Dose escalation phase part 1
- Maximum of 18 subjects or Dose escalation phase part 2
- 24-34 subjects per Dose expansion cohort
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
- •Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling, and analyses.
- •Aged at least 18 years as of the date of consent.
- •Unresectable Stage III or Stage IV melanoma patients, who have had disease progression on or after at least one prior ICI containing treatment. Patients with mucosal and uveal melanoma types are to be excluded.
- •There is at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Estimated life expectancy of a minimum of 12 weeks.
- •Subjects with acquired immune checkpoint inhibitors resistance (objective response or SD>6 months).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at ICF signature.
- •Females should be using adequate contraceptive measures until 180 days after the end of treatment, should not be breastfeeding.
- •Male subjects should be willing to use barrier contraception, ie condoms, for the duration of the study and 180 days after the final dose of study treatment.
- •Subjects should have adequate organ function.
排除标准
- •Primary central nervous system disease, central nervous system metastatic disease, leptomeningeal disease, metastatic cord compression or carcinomatous meningitis.
- •Prior exposure to a CD73 inhibitor/antibody or adenosine receptor inhibitor.
- •Patients considered to have rapidly progressive disease (from the starting of prior line therapy to disease progression lasting no more than 90 days).
- •Prior therapy with any chemotherapy, immunotherapy, anticancer agents or investigational products from a previous clinical study within 28 days of the first dose of study treatment or within a period during which the investigational product or systemic anticancer treatment has not been cleared from the body.
- •Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with a limited field of radiation for palliation within 14 days of the first dose of study treatment. Subject must have recovered from all radiation related toxicity, not requiring corticosteroids.
- •Prior major surgery (excluding placement of vascular access) within 28 days of the first dose of study treatment or minor surgical procedures ≤7 days.
- •Except for alopecia, platinum-induced peripheral neurotoxicity (≤Grade 2). Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE 5.0) Grade 1 at the time of ICF signature.
- •Received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.
- •Subjects receiving unstable or increasing doses of corticosteroids.
- •As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension defined as a blood pressure (BP) ≥160/100 mmHg despite medical therapy, unstable or uncompensated respiratory and renal disease, active bleeding diseases, allogeneic stem cell transplantation, or any solid organ transplant, etc.
研究组 & 干预措施
ATG-037+Keytruda(Pembrolizumab, MK-3475)
Experimental
Part I: Dose Escalation Phase of ATG-037 Monotherapy PartII: Dose Escalation Phase and Dose Expansion Phase of ATG-037 in Upfront Combination with Keytruda(Pembrolizumab, MK-3475)
干预措施: ATG-037 (Drug)
ATG-037+Keytruda(Pembrolizumab, MK-3475)
Experimental
Part I: Dose Escalation Phase of ATG-037 Monotherapy PartII: Dose Escalation Phase and Dose Expansion Phase of ATG-037 in Upfront Combination with Keytruda(Pembrolizumab, MK-3475)
干预措施: KEYTRUDA ®( Pembrolizumab) (Drug)
结局指标
主要结局
DLT
时间窗: Up to 21 Days
Number of Participants with Dose Limiting Toxicity
MTD
时间窗: Up to 21 Days
Maximum tolerated dose of ATG-037
RP2D
时间窗: Up to 21 Days
Recommended phase 2 dose of ATG-037
Incidence of adverse events and server adverse events
时间窗: One year after last patient first dose
Will be graded according to the NCI-CTCAE Grading Scale version 5.0.
次要结局
- Plasma concentration of ATG-037 and derived PK parameters(One year after last patient first dose)
- ORR as per RECIST v1.1 and DOR, DCR, PFS, OS evaluated by the investigators(One year after last patient first dose)
- Inhibition of CD73 enzymatic activity in plasma(One year after last patient first dose)
研究者
研究点 (7)
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