A Phase 1, Open-Label, Multi-center Study Evaluating the Safety and Tolerability of of JMT601 in Participants With Relapsed or Refractory CD20-positive B-cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity(DLT) and maximum tolerated dose(MTD)
研究概览
简要总结
This is a Phase 1, open-label, multi-center study to evaluate the safety of JMT601 in the treatment of relapsed or refractory CD20-positive B-cell non-Hodgkin lymphoma and to determine the recommended dose for Phase 2 studies (RP2D). Study consists of 2 parts. The first part is a dose-escalation part using a 3+3 design with up to 6 dose(0.3 mg/kg, 1 mg/kg, 3 mg/kg, 6 mg/kg, 12 mg/kg and 20 mg/kg) escalation cohorts at increasing levels. The second part is a dose-expansion part at R2PD dose to assess preliminary efficacy of JMT601.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants diagnosed with CD20-positive B-cell non-Hodgkin lymphoma confirmed by histopathology and/or cell biology who have previously received 2 or more lines of therapy
- •Eastern Cooperative Oncology Group (ECOG) physical state score: 0-2
- •Participants must have at least one evaluable or measurable lesion according to Lugano 2014 criteria.
- •Expected survival of at least 3 months;
- •Suitable organ and hematopoietic function:
- •The absolute count of neutrophil (ANC) ≥1.0×109/L;
- •Platelets ≥75×10^9/L (if bone marrow invasion doesn't exist)/≥50.0×10^9/L (if bone marrow invasion exists);
- •Hemoglobin ≥90 g/L;
- •Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min;
- •Total bilirubin ≤1.5×ULN, alanine aminotransferase ≤2.5×ULN, aspartate aminotransferase ≤2.5×ULN; Subjects with liver lesion: TBIL≤3×ULN, ALT≤5×ULN, AST≤5×ULN;
- •International Standardized ratio and activated partial thromboplastin time ≤1.5 × ULN;
排除标准
- •Confirmed central nervous system (CNS) lymphoma.
- •Subjects who have received allogeneic hematopoietic stem cell transplantation (HSCT) or other organ transplantation
- •Those who have previously received targeted CD47 or signal regulatory protein α (SIRRP α) therapy.
- •Previous or current hemolytic anemia, Evans syndrome, arteritis;
- •Subjects with previous or current other malignant tumors;
- •Previous or current history of active autoimmune diseases;
- •Subjects who had undergone major surgery within 4 weeks prior to initial dosing or expected to have major surgery during the study period;
- •HIV infection, active syphilis, hepatitis B surface antigen (HBsAg) positive and HBV-DNA higher than the lower limit or 1000 copies /ml(500 IU/ml), HCV antibody positive and HCV-RNA higher than the lower limit or 1000 copies /ml
研究组 & 干预措施
JMT601
Subjects will receive JMT601 once a week. The first 4-week period is for DLT observation.
Dose escalation part will be carried out according to 3+3 dose-escalation design with up to 6 dose(0.3 mg/kg, 1 mg/kg, 3 mg/kg, 6 mg/kg, 12 mg/kg and 20 mg/kg) escalation cohorts.
Dose expansion part will continue at the determined RP2D. Dose expansion part consists of two cohorts:
Cohort A: Subjects with CD20-positive diffuse large B-cell lymphoma, prior at least two lines of therapy.
Cohort B: Subjects with CD20-positive follicular lymphoma, prior at least two lines of therapy.
干预措施: JMT601 (Biological)
结局指标
主要结局
Dose-limiting toxicity(DLT) and maximum tolerated dose(MTD)
时间窗: DLTs and MTD: Up to 28 days after the first dose
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: TEAEs: Up to 90 days after last dose
次要结局
- Overall response rate (ORR)(Up to 12 months)
- Duration of response (DOR)(Up to 12 months)
- Progression free survival (PFS)(Up to 12 months)
- Overall survival (OS)(Up to 12 months)
- Aera under the curve from 0 to the last measurable concentration(AUClast)(Up to 12 months)
- Aera under the curve from 0 to the infinite time(AUC0-∞)(Up to 12 months)
- Time to maximum concentration(Tmax)(Up to 12 months)
- Terminal phase half-life(T1/2)(Up to 12 months)
- Clearance(CL)(Up to 12 months)
- Volume(Vd)(Up to 12 months)
- Maximum concentration( Cmax)(Up to 12 months)
- Minimum concentration(Cmin)(Up to 12 months)
- Accumulation ratio(AR)(Up to 12 months)