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 Gynecological Tumors and Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 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, dose-escalation and expansion, non-randomized 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 gynecological tumors and other solid tumors.
详细描述
The study consists of two phases: a dose-escalation phase (Phase Ia) and an expansion cohort 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 gynecological tumors and other solid tumors;
- •Agree to provide archived tumor tissue specimens from the primary or metastatic site 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, with 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 ≤1+ or ≤1000 mg/24h;
- •For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, with serum pregnancy test being negative, and they must not be lactating; all enrolled patients (regardless of male or female) must use adequate barrier contraception throughout the entire treatment period and for 6 months after treatment completion;
- •Trial participants must be able and willing to comply with the visits, treatment plans, laboratory tests, and other study-related procedures specified in the protocol.
排除标准
- •Use of chemotherapy, biological therapy, immunotherapy, or other treatments within 4 weeks or 5 half-lives prior to the first dose;
- •Receipt of immunosuppressive drug therapy within 2 weeks prior to the first dose;
- •History of severe cardiac or cerebrovascular disease;
- •Prolonged QTc interval, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
- •Active autoimmune diseases and inflammatory diseases;
- •Prior occurrence of ≥ Grade 3 toxicity related to anti-angiogenic therapy when receiving such therapy previously;
- •Diagnosis of another solid tumor within 5 years prior to the first dose;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose;
- •Poorly controlled hypertension;
- •Diabetes mellitus with poor glycemic control;
- •History of interstitial lung disease requiring corticosteroid therapy, or currently having ILD, or ≥ Grade 2 radiation pneumonitis;
- •Concurrent pulmonary disease resulting in severe respiratory impairment;
- •Active central nervous system metastases;
- •History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy 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 study drug administration;
- •Pleural, abdominal, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first study drug administration;
- •Imaging findings indicating tumor invasion or encasement of major thoracic blood vessels, pericardium, or heart;
- •Trial participants with clinically significant bleeding or significant bleeding tendency within 4 weeks prior to screening;
- •History of fistula, gastrointestinal perforation, or 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 participation 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)
- 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)
- Anti-drug Antibody (ADA)(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)