A Phase I Study to Evaluate the Tolerability and Pharmacokinetics of TQB3820 in Relapsed or Refractory Multiple Myeloma (R/R MM) or Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma (R/R B-NHL)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 116
- 试验地点
- 2
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
TQB3820 is a novel cereblon-modulating agent. Upon binding to cereblon, a substrate receptor in the cullin4 E3 ligase complex, TQB3820 promotes recruitment, ubiquitination, and subsequent proteasomal degradation of the hematopoietic transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). Modulation of Aiolos and Ikaros expression has the potential to correct multiple aspects of the immune dysregulation mediated by B cells.
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 Multiple Myeloma cohort
- •Patients must have received at least 2 prior therapies;
- •Measurable levels of myeloma paraprotein
- •M-protein in serum >5 g/L;
- •M-protein in urine >200mg/24h;
- •Light chain Multiple Myeloma without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 100 mg/L and abnormal serum immunoglobulin kappa lambda free light chain ratio.
- •For Indolent B-NHL
- •Progressed after standard treatment or no standard treatment with an established survival benefit is available;
- •Imaging in screening showing at least one measurable lesion; In patients with CLL/SLL, circulating lymphocytes >= 5.0 × 10^9/L or lesions greater than 1.5 cm.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
- •Life expectancy >=3 months;
- •Adequate organ/system function;
- •Female patients of childbearing age should agree to use contraceptive measures during the study period and for at least 6 months after study is stopped; male patients should agree to use contraception during the study period and for at least 6 months after study is stopped;
排除标准
- •Patients received allogenic haemopoietic stem cell transplantation, or autologous stem cell transplantation within 3 months;
- •Diagnosed and/or treated additional malignancy within 3 years before the first dose;
- •With factors affecting oral medication;
- •Toxicity that is >=Grade 2 caused by previous cancer therapy;
- •Patients with congenital bleeding or coagulopathy, or are being treated with anticoagulants;
- •Patients with uncontrolled infections;
- •Has received surgery, chemotherapy, radiotherapy or other anticancer therapies 2 weeks before the first dose;
- •Has received Chinese patent medicines with anti-tumor indications that National Medical Products Administration(NMPA) approved within 2 weeks before the first dose;
- •Pleural effusion, pericardial effusion or ascites that cannot be controlled and need repeated drainage;
- •Central nervous system metastases;
- •Has participated in other clinical studies within 4 weeks before the first dose;
- •According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.
研究组 & 干预措施
TQB3820 tablets
TQB3820 tablets are administrated orally on Days 1-28 of each 28-day treatment cycle. Dose escalation of TQB3820 will be based on evaluation of clinical safety and tolerability and guided by accumulating PK data.
干预措施: TQB3820 tablets (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: up to 18 months
DLT describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.
Maximum Tolerated Dose (MTD)
时间窗: up to 18 months
The maximum Dose at which less than 33% subjects experiencing DLT
Recommended Phase II Dose (RP2D)
时间窗: up to 18 months
RP2D will be based on evaluation of clinical safety and tolerability and guided by accumulating pharmacokinetics (PK) data
Adverse Events (AEs)
时间窗: Baseline up to 24 months
Type, frequency, seriousness and severity of adverse events and laboratory abnormalities, such as hyperuricemia.
次要结局
- Maximum (peak) plasma drug concentration (Cmax)(Hour 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on single dose ; Hour 0(pre-dose) of day1, day8, day15, day22 on multiple dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on multiple dose of day28))
- Time to reach maximum(peak )plasma concentration following drug administration (Tmax)(Hour 0(pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on single dose ; Hour 0(pre-dose) of day1, day8, day15, day22 on multiple dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on multiple dose of day28))
- Elimination half-life (t1/2)(Hour 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on single dose ; Hour 0 (pre-dose) of day1, day8, day15, day22 on multiple dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on multiple dose of day28))
- Overall response rate (ORR)(Baseline up to 24 months)
- Clinical benefit rate (CBR)(Baseline up to 24 months)
- Time to response (TTR)(Baseline up to 24 months)
- Duration of Response (DOR)(Baseline up to 24 months)
- Progression-free survival (PFS)(Baseline up to 24 months)
- Overall survival (OS)(Baseline up to 24 months)