A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of SI-B036 Bispecific Antibody Injection in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Phase Ia: Dose limiting toxicity (DLT)
研究概览
简要总结
This study is an open-label, multicenter, non-randomized Phase I clinical study of dose-escalation and expansion to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of SI-B036 bispecific antibody injection in patients with locally advanced or metastatic solid tumors.
详细描述
The study consists of two phases: a dose-escalation phase (Phase Ia) and an expansion phase (Phase Ib).
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 sign the informed consent form and comply with the protocol requirements;
- •No gender restriction;
- •Age: ≥18 years and ≤75 years;
- •Expected survival time ≥3 months;
- •Locally advanced or metastatic solid tumors;
- •Agree to provide archived tumor tissue specimens from primary or metastatic lesions within 2 years or fresh tissue samples;
- •Must have at least one measurable lesion as defined by RECIST v1.1;
- •ECOG performance status score of 0 or 1;
- •Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
- •Organ function levels must meet the requirements;
- •Coagulation function: International Normalized Ratio ≤1.5, and Activated Partial Thromboplastin Time ≤1.5 × ULN;
- •Urine protein ≤2+ or ≤1000 mg/24h;
- •For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum pregnancy must be negative, and they must be non-lactating; all enrolled patients (regardless of male or female) must adopt adequate barrier contraceptive measures throughout the entire treatment period and for 6 months after treatment completion;
- •The trial participant is capable and willing to adhere to the visit schedule, treatment plan, laboratory tests, and other study-related procedures specified in the protocol.
排除标准
- •Use of chemotherapy, biological therapy, immunotherapy, etc. within 4 weeks or 5 half-lives prior to the first dose;
- •Receipt of immunosuppressive therapy within 2 weeks prior to the first dose;
- •History of severe cardiac or cerebrovascular disease;
- •QT interval prolongation, complete left bundle branch block, etc.;
- •Active autoimmune diseases and inflammatory diseases;
- •Prior experience of ≥ grade 3 toxicity related to anti-angiogenic therapy during previous anti-angiogenic treatment;
- •Diagnosis of another solid tumor within 5 years prior to the first dose;
- •Unstable thrombotic event requiring therapeutic intervention within 6 months prior to the first dose;
- •Poorly controlled hypertension;
- •Diabetic patients with poorly controlled blood glucose;
- •History of ILD requiring steroid therapy, or current ILD, or ≥ grade 2 radiation pneumonitis;
- •Concomitant pulmonary disease causing severe respiratory impairment;
- •Active central nervous system metastases;
- •History of allergy to recombinant humanized or human-mouse chimeric antibodies, or hypersensitivity to any excipient component of SI-B036;
- •Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
- •Positive for human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •Active infection requiring systemic therapy within 4 weeks prior to the first dose of study drug;
- •Presence of pleural, abdominal, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first dose of study drug;
- •Imaging findings indicating tumor invasion or encasement of major thoracic blood vessels, pericardium, or heart;
- •Study participants with clinically significant bleeding or a clear bleeding tendency within 4 weeks prior to screening;
- •History of fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to the first dose;
- •Use of another investigational drug within 4 weeks or 5 half-lives prior to the first dose;
- •Pregnant or breastfeeding women;
- •Other conditions deemed by the investigator to make the participant unsuitable for enrollment in this clinical trial.
研究组 & 干预措施
SI-B036
Participants receive SI-B036 for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
干预措施: SI-B036 (Drug)
结局指标
主要结局
Phase Ia: Dose limiting toxicity (DLT)
时间窗: Up to 21 days after the first dose
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Phase Ia: Maximum tolerated dose (MTD)
时间窗: Up to 21 days after the first dose
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle.
Phase Ib: Recommended Phase II Dose (RP2D)
时间窗: Up to approximately 24 months
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of SI-B036.
次要结局
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Progression-free survival (PFS)(Up to approximately 24 months)
- Objective Response Rate (ORR)(Up to approximately 24 months)
- Disease Control Rate (DCR)(Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- CL (Clearance)(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
- ADA (anti-drug antibody)(Up to approximately 24 months)