A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-ARC002 Injection in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 22
- 试验地点
- 1
- 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 BL-ARC002 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 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 —（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 and ≤75 years (Phase Ia); ≥18 years (Phase Ib);
- •Expected survival ≥3 months;
- •Locally advanced or metastatic esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, or other solid tumors;
- •Agree to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions obtained within 2 years;
- •Must have at least one measurable lesion as defined by RECIST v1.1;
- •Eastern Cooperative Oncology Group (ECOG) performance status 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-specified 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 pregnancy test must be performed within 7 days prior to the start of treatment, with a negative serum pregnancy test result, and they must be non-lactating; all study participants (both male and female) must use adequate barrier contraception throughout the entire treatment period and for 7 months after the completion of treatment.
排除标准
- •Use of chemotherapy, biotherapy, immunotherapy, or other anti-tumor therapies within 4 weeks or 5 half-lives prior to the first dose;
- •History of severe cardiac disease;
- •QT interval prolongation, complete left bundle branch block, or third-degree atrioventricular block;
- •Active autoimmune diseases and inflammatory diseases;
- •Diagnosis of another malignant tumor within 5 years prior to the first dose;
- •Hypertension inadequately controlled by two antihypertensive agents;
- •History of interstitial lung disease (ILD) requiring corticosteroid therapy, or current ILD, or radiation pneumonitis of Grade ≥2;
- •Active central nervous system (CNS) metastases;
- •Subjects with a history of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of BL-ARC002;
- •Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
- •Cumulative anthracycline dose > 360 mg/m² from prior (neo)adjuvant anthracycline-based therapy;
- •Positive for human immunodeficiency virus (HIV) antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •Active infection requiring systemic therapy;
- •Participation in another clinical trial within 4 weeks prior to the first dose;
- •Pregnant or breastfeeding women;
- •Subjects with claustrophobia or inability to lie flat for the duration of required examinations due to various reasons;
- •Any other conditions that, in the investigator's judgment, make the subject unsuitable for participation in this clinical trial.
研究组 & 干预措施
BL-ARC002
Participants receive BL-ARC002 for the first cycle (6 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: BL-ARC002 (Drug)
结局指标
主要结局
Phase Ia: Dose limiting toxicity (DLT)
时间窗: Up to 42 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 42 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 BL-ARC002.
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)
- ADA (anti-drug antibody)(Up to approximately 24 months)
- Radiation Characteristics(Up to approximately 24 months)
- Phase Ib: Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase Ib: Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase Ib: Duration of Response (DOR)(Up to approximately 24 months)