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 Head and Neck 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
- 2
- 主要终点
- Phase Ia: Dose limiting toxicity (DLT)
研究概览
简要总结
This is an open-label, multicenter, 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 head and neck 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 agree to comply with the protocol requirements;
- •No gender restriction;
- •Age: ≥18 years and ≤75 years;
- •Life expectancy ≥3 months;
- •Locally advanced or metastatic head and neck tumors and other solid tumors;
- •Agree to provide archived tumor tissue specimens or fresh tissue samples from the primary or metastatic lesions within 2 years;
- •Must have at least one measurable lesion as defined by RECIST v1.1;
- •ECOG performance status score of 0 or 1;
- •Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
- •No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
- •Organ function levels must meet the protocol requirements;
- •Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN);
- •Urine protein ≤2+ or ≤1000 mg/24h;
- •For premenopausal women of childbearing potential, a serum pregnancy test must be performed within 7 days prior to the start of treatment, with a negative result, and they must not be lactating. All enrolled patients (regardless of gender) must adopt adequate barrier contraceptive measures throughout the entire treatment period and for 6 months after the completion of treatment;
- •Participants must be capable of and willing to comply with the study visits, treatment plans, laboratory tests, and other study-related procedures as specified in the protocol.
排除标准
- •Received chemotherapy, biotherapy, immunotherapy, or other systemic anti-tumor therapies within 4 weeks or 5 half-lives prior to the first dose;
- •Received immunosuppressive medications 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;
- •History of ≥ Grade 3 toxicity related to anti-angiogenic therapy when previously receiving such treatment;
- •Diagnosis of another solid malignancy within 5 years prior to the first dose;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose;
- •Uncontrolled hypertension;
- •Diabetes mellitus with poor glycemic control;
- •History of interstitial lung disease (ILD) requiring corticosteroid therapy, or current ILD, or ≥ Grade 2 radiation pneumonitis;
- •Concurrent pulmonary disease resulting in severe impairment of respiratory function;
- •Active central nervous system (CNS) metastases;
- •History of allergy to recombinant humanized or human-mouse chimeric antibodies, or allergy to any excipient of SI-B036;
- •Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
- •Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus (HBV) infection, or active hepatitis C virus (HCV) infection;
- •Active infection requiring systemic therapy within 4 weeks prior to the first dose of study drug;
- •Pleural, abdominal, pelvic, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first dose of study drug;
- •Imaging findings indicate that the tumor has invaded or encased the great thoracic vessels, pericardium, or heart;
- •Clinically significant hemorrhage or obvious 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 lactating women;
- •Any other conditions that, in the investigator's judgment, 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)
- 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)