A Multicenter, Open-label Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Dosimetry and Efficacy of SKB107 in Subjects With Advanced Solid Tumors With Bone Metastases
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Incidence and severity of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
研究概览
简要总结
A multicenter, open-label Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, dosimetry and efficacy of SKB107 in subjects with advanced solid tumors with bone metastases.
详细描述
This study is a multicenter, open-label Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, dosimetry and efficacy of SKB107 in subjects with advanced solid tumors with bone metastases. The study is divided into two parts: Phase Ia and Phase Ib. The Phase Ia study is the dose escalation phase. The primary objective is to assess the safety and tolerability of a single administration of SKB107 and to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) based on the occurrence of Dose-Limiting Toxicities (DLTs) associated with SKB107 (if the MTD cannot be determined).The Phase Ib study is the dose expansion phase. The primary objective is to explore the optimal dose, safety, or efficacy of SKB107 at a selected dose level (confirmed as safe by the Safety Review Committee (SRC) and not exceeding the MTD or MAD)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •The age should be between 18 years and 75 years at the time of signing the informed consent form (ICF);
- •The Eastern Cooperative Oncology Group (ECOG) performance status score should be ≤ 1;
- •The expected survival period should be ≥ 3 months;
- •Phase Ia: Subjects with advanced solid tumor bone metastases diagnosed by histology or cytology; and the subjects have failed standard treatment, or have no standard treatment, or are intolerant or not applicable to standard treatment;
- •Phase Ib: Subjects with advanced mCRPC diagnosed by histology or cytology;
- •Before the first administration, a 99mTc-MDP bone scan diagnosed multiple bone metastases, and at least one site was confirmed by CT or MRI;
- •Have adequate organ and bone marrow functions;
- •For subjects with reproductive capacity, take effective medical contraceptive measures during the study treatment and within 6 months after the last administration;
- •The subjects voluntarily join this study, sign the informed consent form, and can comply with the visit and related procedures stipulated in the protocol.
排除标准
- •The washout period before the first administration of the study drug was insufficient.
- •Previous received similar radionuclide internal irradiation treatment.
- •Previous received or planned to receive during the study period semi-body external radiotherapy targeting bone metastases.
- •Known "super bone imaging".
- •Known spinal cord compression, or clinical imaging manifestations suggesting impending spinal cord compression.
- •Any cardiovascular or cerebrovascular diseases or cardiovascular risk factors that may affect the treatment of the study drug.
- •Poorly controlled diabetes and hypertension.
- •The toxicity of previous anti-tumor treatment before the first administration has not recovered to ≤ 1 grade (evaluated based on NCI-CTCAE v5.0) or has not reached the level specified in the inclusion/exclusion criteria.
- •Had other malignant tumors within 3 years before the first administration.
- •Subjects with severe and/or uncontrolled concomitant diseases.
- •Active hepatitis B or active hepatitis C.
- •Human immunodeficiency virus (HIV) test positive or having a history of acquired immune deficiency syndrome (AIDS); known active syphilis infection.
- •Subjects with a history of radionuclide/radioactive drug allergy, or allergic to any component of the study formulation.
- •During the screening process before the first administration, the condition deteriorated rapidly, such as significant changes in the investigator's assessment of physical condition, etc.
- •Subjects participating in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an intervention study.
- •Any unstable disease or clinical condition, or any condition that may endanger the safety of the subject or affect the subject's compliance, or any other conditions that the investigator deems inappropriate for participation in this study.
研究组 & 干预措施
Phase 1a：Dose escalation
5 dose levels are tentatively planned for Phase 1a
干预措施: SKB107 for injection (Drug)
Phase 1b: Dose expansion
The dose of SKB107 for injection in Phase 1b is selected based on the Phase 1a monotherapy dose escalation study
干预措施: SKB107 for injection (Drug)
结局指标
主要结局
Incidence and severity of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
时间窗: Up to 3 year
次要结局
- Maximum plasma concentration (Cmax) of SKB107(Up to 1 week)
- Dosimetry(Up to 1 week)
- Time to Radiographic Bone Progresion (TTRBP)(Through study completion, an average of 1 year.)
- Radiographic progression-free survival (rPFS)(Through study completion, an average of 1 year)
- Overall survival(OS)(Up to 3 years)
- symptomatic skeletal event-free survival (SSE-FS)(Up to 3 years)