Phase I Clinical Trial to Evaluate the Tolerability and Pharmacokinetics of TQB2223 Injection Combined With Penpulimab Injection in Subjects With Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 92
- 试验地点
- 11
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
TQB2223 is a recombinant, fully humanized antibody that binds lymphocyte activation gene-3 (LAG-3) and blocks the LAG-3/ major histocompatibility complex class II (MHC-II) interaction, thus allowing for increased T-cell proliferation and cytokine production. This is a phase I study to evaluate the safety, tolerability, pharmacokinetics (PK) and effectiveness of TQB2223 injection in combination with Penpulimab in subjects with advanced cancers.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study;
- •Male or female patient 18 to 75 years of age, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and life expectancy ≥3 months;
- •Histologically or cytologically confirmed malignancies;
- •Subjects with advanced malignant tumors who failed standard treatment or lacked effective treatment;
- •Patient has at least one evaluable lesion assessed by RECIST 1.1;
- •The main organs function is well;
- •Male or female patient had no plans to become pregnant and voluntarily take effective contraceptive measures during study period until at least 6 months after the last dose of study drug.
排除标准
- •Concurrent secondary malignancy. or other malignancy with no evidence of disease for more than 5 years;
- •History of uncontrolled intercurrent illness;
- •Major surgical procedure, radiotherapy, chemotherapy, or immunotherapy within 4 weeks prior to first dose;
- •Prior treatment targeting LAG-3;
- •Unstable or serious concurrent medical conditions, as assessed by the Investigators, that would substantially increase the risk-benefit ratio of participating in the study.
研究组 & 干预措施
TQB2223 injection+ Penpulimab Injection
intravenous injection of TQB2223 injection and Penpulimab injection for one times every three weeks, 21 days as a treatment cycle.
干预措施: TQB2223 injection+ Penpulimab Injection (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: During the first treatment cycle (21 days).
DLT is defined as toxicities that meet pre-defined severity criteria of Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and assessed as having a suspected relationship to TQB2223 injection, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle (21 days) of treatment.
Maximum tolerated dose (MTD)
时间窗: During the first treatment cycle (21 days).
MTD was defined as the highest dose at which dose-limiting toxicity (DLT) occurred in less than 33% of patients.
Objective Response Rate (ORR)
时间窗: From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks.
Defined as the percentage of Complete Response (CR) plus partial response (PR) assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria and Guidelines for Response Criteria for Use in Trials Testing Immunotherapeutics (iRECIST) for solid tumors, Lugano 2014 criteria and Lymphoma Response to Immunomodulatory therapy Criteria (LYRIC) for lymphoma.
次要结局
- Terminal half-life (T1/2)(5 minutes, 2 hour, 6 hours, 24 hours, 144 hours and 336 hours after dose on cycle 1 and cycle 3. Pre-dose on cycle 2, 4, 5, 6, 7, 8. Each cycle is 21 days.)
- Receptor occupation (RO)(5 minutes, 2 hour, 6 hours, 24 hours, 144 hours and 336 hours after dose on cycle 1 and cycle 3. Pre-dose on cycle 2, 4, 5, 6, 7, 8. Each cycle is 21 days.)
- Objective Response Rate (ORR)(From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks)
- Number of patients with adverse events (AEs)(From the time of informed consent signed to 28 days after the last dose)
- The area under the curve (AUC)(5 minutes, 2 hour, 6 hours, 24 hours, 144 hours and 336 hours after dose on cycle 1 and cycle 3. Pre-dose on cycle 2, 4, 5, 6, 7, 8. Each cycle is 21 days.)
- Disease control rate (DCR)(From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks)
- Progression-free survival (PFS)(From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks)
- Percentage of anti-drug antibody (ADA) positive patients(Pre-dose on Cycle 1, 2, 4, 8 . 30 days and 90 days after the last dose. Each cycle is 21 days.)
- Peak concentration (Cmax)(5 minutes, 2 hour, 6 hours, 24 hours, 144 hours and 336 hours after dose on cycle 1 and cycle 3. Pre-dose on cycle 2, 4, 5, 6, 7, 8. Each cycle is 21 days.)
- Duration of Response (DOR)(From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks)
- Overall survival (OS)(From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks)
- Number of patients with serious adverse events (SAEs)(From the time of informed consent signed to 28 days after the last dose)