An Open-label, Multicenter, Phase I Safety Study of AXT-1003 in Subjects With Advanced Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 5
- 主要终点
- Number of Participants With Dose-Limiting Toxicity (DLT) (Dose Escalation)
研究概览
简要总结
This is a Phase I study of AXT-1003 to assess the safety, tolerability, and pharmacokinetics in patients with advanced malignancies.
详细描述
AXT1003-1102 is a multicenter, open-label, Phase I safety study of AXT-1003 in patients with advanced malignancies. It is designed to observe the safety of AXT-1003 in patients with advanced malignancies, determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), evaluate the pharmacokinetic profile, and explore the preliminary antitumor activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •For Ia dose escalation part only:
- •R/R NHL: Locally histopathological diagnosis of relapsed/refractory non-Hodgkin lymphoma (R/R NHL), who have progressed or been intolerant after the available standard therapies, or have no access to the standard therapies.
- •Advanced solid tumors: Locally histopathological diagnosis of locally advanced unresectable and metastatic solid tumors,The above subjects have progressed or been intolerant after the available standard therapies, or have no access to the standard therapies.
- •For Ib dose expansion part only: Subjects with relapsed/refractory peripheral T-cell lymphoma (R/R PTCL)
- •Eastern Cooperative Oncology Group (ECOG) performance status scale 0 to
- •Have a life expectancy of at least 3 months.
- •For Ib dose expansion part and not mandatory for Ia dose escalation part: Subjects with R/R NHL must have measurable lesions as defined by Lugano 2014 criteria. Subjects with advanced solid tumors must have measurable or evaluable lesions as defined by RECIST 1.
- •Adequate organ and bone marrow functions.
- •The adequate washout period for prior therapy .
- •Subjects must use a highly effective contraception method throughout the study and for 3 months after discontinuation of the study drug.
- •Signed ICF and willing to comply with all the requirements in the protocol.
排除标准
- •Diagnosis of precursor B-cell lymphoblastic leukemia/lymphoma, precursor T-cell lymphoblastic leukemia/lymphoma, precursor NK cell lymphoblastic leukemia/lymphoma. Diagnosis of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL).
- •Central nervous system infiltration.
- •Uncontrolled or significant cardiovascular disease.
- •Major surgery within 4 weeks before the first dose of study drug.
- •Known or suspected hypersensitivity to AXT-1003 or any of the excipients.
- •Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of AXT-
- •History of other malignancies prior to enrollment; except for subjects with basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or other carcinomas in situ who have undergone possible curative treatment and do not have disease recurrence within 5 years since starting the treatment.
- •Any prior treatment-related clinically significant toxicities that have not resolved to Grade ≤ 1 or prior treatment-related toxicities that are clinically unstable and clinically significant at time of enrollment.
- •Active infection requiring systemic treatment.
- •Infection with hepatitis B virus with positive hepatitis B surface antigen, or hepatitis C virus with detectable anti-hepatitis C circulating viral RNA.
- •Subjects known to be infected with human immunodeficiency virus and active tuberculosis.
- •Females who are pregnant or breastfeeding.
研究组 & 干预措施
AXT-1003
Dose Escalation: Part A:
Level 1 (Starting Dose) Oral AXT-1003 5 mg BID; Level 2 Oral AXT-1003 10mg BID; Level 3 Oral AXT-1003 15mg BID ; Level 4 Oral AXT-1003 20mg BID; Level 5 Oral AXT-1003 25mg BID; Level 6 Oral AXT-1003 30mg BID; Level 7 Oral AXT-1003 35mg BID; Level 8 Oral AXT-1003 40mg BID;
Dose Escalation: Part B:
Oral AXT-1003 2.5mg QD, 10mg BID;
Dose Expansion: 1 or 2 cohorts at the dose levels selected from dose escalation part
干预措施: AXT-1003 (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicity (DLT) (Dose Escalation)
时间窗: Up to 28 days
Dose Escalation only: to characterize the dose limiting toxicities (DLTs) of AXT-1003.
Number of Participants with Adverse Events (AEs)
时间窗: Baseline up to 30 days after the last dose of study
Laboratory test ,ECG, vital signs, physical examination
次要结局
- Overall response rates (ORR)(Up to 3 years)
- Duration of response(DOR)(Up to 3 years)
- Progression free survival (PFS)(Up to 3 years)
- Time to response (TTR)(Up to 3 years)
- Disease control rate (DCR)(Up to 3 years)
- Maximum observed concentration (Cmax) of AXT-1003(Up to 15 days)
- Time of maximum observed concentration (tmax) of AXT-1003(Up to 15 days)
- Area under the curve from the time of dosing to the time of the last measurable concentration (AUCtau) of AXT-1003(Up to 15 days)
- Minimum observed concentration (Cmin) of AXT-1003(Up to 15 days)
- Terminal elimination half-life (t1/2) of AXT-1003(Up to 15 days)
- Total body clearance (CL/F) of AXT-1003(Up to 15 days)