A Phase I Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SIBP-A10 Injection in the Treatment of Advanced Malignant Tumor Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- AE (Adverse Events)
研究概览
简要总结
To evaluate the safety, tolerability of SIBP-A10 and determine the maximum tolerable dose (MTD) and phase II recommended dose (RP2D).
详细描述
This study is an open label, dose escalation, dose expansion, and indication expansion study to evaluate safety, tolerability, pharmacokinetics, preliminary anti-tumor efficacy, immunogenicity, impact on QT/QTc interval, and explore potential biomarkers of SIBP-A10 for injection in subjects with advanced metastatic tumors.
This study is divided into three stages and is planned to be set up seven dose groups, including 0.5, 1.5, 3, 5, 7, 10 and 15 mg/kg. The first stage is the dose escalation stage, which will start from the first and second doses for enrollment. If necessary, a 3+3 dose escalation design will be used. At least 19 subjects will be enrolled, and the specific sample size should be adjusted according to the subjects' tolerance level. The second stage is the dose expansion stage, where two or more doses are selected to enter the dose expansion phase, and at least 20 subjects will be enrolled in each dose group for dose expansion. The third stage is the indication expansion stage, where phase II recommended dose (RP2D) is preliminarily determined based on the escalation and expansion of dosage in the early stage. Using RP2D for indication expansion, we plan to expand four indication cohorts, with at least 40 subjects selected for each cohort.
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
- •Voluntarily participate in this study and sign an informed consent form;
- •Age range of 18 to 75 years old (including boundary values), gender not limited;
- •The clinical diagnosis of enrolled subjects should meet the conditions specified in the protocol:
- •There must be at least one measurable lesion as the target lesion;
- •Backfilling queue during dose escalation stage, dose expansion stage, and indication expansion stage: able to provide tumor tissue samples that meet the requirements of the protocol or undergo tumor biopsy during screening, or provide testing reports issued by legitimate testing institutions that meet the requirements;
- •I have not received any medication targeting Siglec-15 in the past;
- •The Eastern Cooperative Oncology Group (ECOG) physical fitness score ranges from 0 to 1;
- •Expected survival period ≥ 3 months;
- •During the screening period, the main organ functions were basically normal;
- •During the screening period, women of childbearing age had negative blood pregnancy tests, and reproductive age subjects (including male subjects) had no pregnancy plans during the trial period and within 6 months after the last dose, and voluntarily took effective contraceptive measures.
排除标准
- •The subject has the following tumors:
- •The subject has had other malignant tumors that have not healed within the past 5 years;
- •Subjects with meningeal metastases;
- •Subjects with active brain metastases;
- •For anti-tumor subjects with a history of past treatment or surgery that does not comply with the protocol, or who have received treatment that does not comply with the protocol during the planned trial period
- •Previous medical history or laboratory non-compliance with protocol requirements
- •According to the researchers' assessment, the screening period is accompanied by severe, progressive, or uncontrolled non-tumor diseases, and it has been determined by the researchers that participating in the study would increase the risk for the subjects.
- •According to the investigator's judgment, there are concomitant diseases (including but not limited to hypertension, diabetes, active infection, etc. that cannot be controlled by drugs) that seriously endanger the patient's safety or affect the patient's completion of the study
- •Researchers determine that there are uncontrollable ascites, pleural effusion, or pericardial effusion, or those who have undergone ≥ 2 serosal drainage within 2 weeks prior to the first administration;
- •Before starting treatment, the patient has not yet recovered to ≤ grade 1 from the toxic effects of previous treatments (including previous immunotherapy) and/or complications of previous surgical interventions.
- •Individuals with a history of severe allergies to protein products, CHO cell products, other recombinant human or humanized antibodies, or components of the investigational drug;
- •Pregnant and lactating women;
- •Researchers believe that subjects who are not suitable to participate in this clinical study due to other reasons.
研究组 & 干预措施
Experimental group
The subjects enrolled will be sequentially assigned to the corresponding dose level.
干预措施: SIBP-A10 (Drug)
结局指标
主要结局
AE (Adverse Events)
时间窗: From day 1 after the first dose to day 28 after the last dose
That is adverse events, any adverse events that occurred to the subject during the study period.
Phase II recommended dose (RP2D)
时间窗: Day 21 after the last dose in the dose expansion phase
RP2D refers to the recommended dose determined through initial dose escalation and toxicity assessment in clinical trials, used for further evaluation of drug efficacy and safety.
Dose-limiting toxicity (DLT)
时间窗: Day 21 after each dose in the dose escalation stage
DLT is defined as any adverse event related to the drug defined in the protocol that occurs within 21 days of the first cycle after a single administration.
Maximum tolerated dose (MTD)
时间窗: Day 21 after the last dose in the dose escalation stage
MTD is defined as the maximum dose at which the number of DLT cases occurring during the DLT observation period within 21 days after a single administration is ≤ 1/6 of the total number of cases.
次要结局
- AUC (Area Under The Plasma Concentration Versus Time Curve)(Day 1, Day 22 and Day 64 after the first dose)
- Cmax (Peak Plasma Concentration)(Day 1, Day 22 and Day 64 after the first dose)
- Tmax (Peak Time)(Day 1, Day 22 and Day 64 after the first dose)
- ORR (Objective Response Rate)(6 weeks after the last evaluation)
- DCR (Disease control rate)(6 weeks after the last evaluation)
- PFS (Progression-free survival)(6 weeks after the last evaluation)
- OS (overall survival)(From the first injection to 36 months after the first injection.)