A Phase I Clinical Study to Characterize Safety, Tolerability, and Pharmacokinetics of TR115 in Patients With Relapsed / Refractory Non-Hodgkin's Lymphoma or Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Adverse events and serious adverse events
研究概览
简要总结
A phase 1 dose escalation and expanded cohort study of TR115 in the treatment of adult patients with relapsed/refractory non-hodgkin's lymphoma or advanced solid tumors.
详细描述
This is a open-label, dose escalation and expansion, accelerated titration combined 3+3 design, phase 1 study, to evaluate the safety and tolerability, and to determine the Recommeded Phase II Dose (RP2D) of TR115 when administered bid in patients with non-hodgkin's lymphoma or advanced solid tumors. During the dose escalation phase, Up to 6 cohorts of 1-6 0r 3-6 patients each will be treated in the study.
Patients will receive study treatment until criteria for study termination are met. A safety Follow-up Visit will conducted 30 days (±7 days) after the last dose of treatment. Patients who discontinue study treatment for reasons other than disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, lost to follow-up, death, or until the sponsor stops the study, whichever comes first.
After finishing the dose escalation phase, a dose extension phase will be initiated with additional patients included in order to further evaluate the tolerability, pharmacokinetics, and efficacy at the recommended dose that have been evaluated in the dose escalation phase.
Adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.
Tumor response will be assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) scan using Lugano 2014/RECIST 1.1 criteria, assessed by the investigator.
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
- •fully understand the procedures of the clinical study and participate voluntarily with signed and dated written informed consent form, comply with the requirements of the study protocol.
- •males and/or females at least 18 years old when signing the informed consent form.
- •tumor type criteria:
- •relapsed/refractory histologically or cytologically documented non-hodgkin's lymphoma must have received at least 1 prior systemic therapies, including but not limited as below: Follicular Lymphoma (FL), Diffuse Large B-cell Lymphoma (DLBCL), Peripheral T-cell lymphoma-Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell Lymphoma (AITL), Anaplastic Large Cell Lymphoma (ALCL).
- •histologically or cytologically confirmed patients with advanced malignant solid tumors, eligible patients must have failed standard treatment, no standard treatment, or not suitable for standard treatment at this stage as determined by the investigator.
- •eastern cooperative oncology group performance status (ECOG) ≤2 at screening.
- •life expectancy of at least 3 months.
- •acceptable organ function: absolute neutrophil count (ANC)≥1.0×109/L (note: growth factor supports within 14 days of the first dose); platelet count (PLT)≥90×109/L （note: PLT≥70 × 109/L for patients with Non-Hodgkin Lymphoma (NHL) and ≥50 × 109/L allowed in patients with bone marrow infiltration. no blood product transfusion is allowed within 14 days of the first dose); hemoglobin (Hb) ≥90g/L (note: Hb ≥80g/L for patients with NHL and ≥70g/L in patients with bone marrow infiltration. no blood product transfusion is allowed within 14 days of the first dose); International Normalized Ratio (INR) or Prothrombin Time (PT)≤1.5×Upper limit of normal value (ULN), Activated Partial Thromboplastin Time (APTT)≤1.5×ULN ；Total bilirubin (TBIL)≤1.5×ULN, Aspartate Amino Tranferase (AST) and Alanine Transaminase (ALT)≤2.5×ULN (note: ≤ 5 × ULN if there is liver involvement); Creatinine (Cr) ≤1.5×ULN or Creatinine Clearance (CCr) ≥50 ml/min (calculated by Cockcroft-Gault formula).
- •fertile male and female must agree to use medically approved contraceptives during the study and within 6 months after the last dose of the study.
排除标准
- •known or suspected allergies to any of the investigational drug compositon.
- •medical history and surgical history excluded according to the protocol.
- •any previous medical treatment history exclude from the protocol.
- •abnormal laboratory results exclude from the protocol.
- •pregnant and lactating women (currently breast-feeding or less than six months after delivery although not breast-feeding).
- •subjects may not be able to complete the study due to poor compliance or other reasons, or unsuitable for the study by the investigator's judgment.
研究组 & 干预措施
Dose Escalation and Expansion
Participants with relapsed/Refractory Non-Hodgkin's Lymphoma or Advanced solid tumor will receive TR115 at escalating and expansion dose levels.
干预措施: TR115 (Drug)
结局指标
主要结局
Adverse events and serious adverse events
时间窗: from the first dose to within 30 days after the last dose
frequency, duration and severity of adverse events and serious adverse events evaluated by NCI CTCAE 5.0
dose limited toxicities
时间窗: within 31 days after the first dose
incidence of dose limited toxicities
recommedded phase 2 dose
时间窗: Throughout the study for approximately 2 years
evaluated by safety review committee
maximum tolerated dose
时间窗: Throughout the study for approximately 2 years
evaluated by safety review committee
次要结局
- AUClast(within 31 days after the first dose)
- Cmax(within 31 days after the first dose)
- Tmax(within 31 days after the first dose)
- Vz/F(within 31 days after the first dose)
- AUCinf(within 31 days after the first dose)
- CL/F(within 31 days after the first dose)
- Terminal half-life (T1/2)(within 31 days after the first dose)