A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Lutetium [177Lu] BL-ARC001 Injection in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Phase Ib: Recommended Phase II Dose (RP2D)
研究概览
简要总结
This study is an open-label, multicenter, non-randomized Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of Lutetium [177Lu] BL-ARC001 in patients with locally advanced or metastatic solid tumors.
详细描述
The study is divided into two phases: a dose escalation phase (Phase Ia) and a cohort 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 —（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;
- •Gender: no restriction;
- •Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib);
- •Expected survival time ≥3 months;
- •Locally advanced or metastatic solid tumors;
- •Agree to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions within the past 3 years;
- •Must have at least one measurable lesion meeting the RECIST v1.1 criteria;
- •ECOG performance status score of 0 or 1;
- •Toxicities from prior antitumor therapy have recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
- •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 ≤1000mg/24h;
- •For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum pregnancy must be negative, and must not be breastfeeding; all enrolled patients (regardless of gender) should use adequate barrier contraception throughout the treatment cycle and for 6 months after treatment ends.
排除标准
- •Use of chemotherapy, biotherapy, or immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose;
- •History of severe heart disease;
- •QT interval prolongation, complete left bundle branch block, or third-degree atrioventricular block;
- •Active autoimmune or inflammatory diseases;
- •Diagnosis of other malignancies within 5 years prior to the first dose;
- •Hypertension poorly controlled by two antihypertensive medications;
- •History of interstitial lung disease (ILD) requiring steroid treatment, current ILD, or ≥ Grade 2 radiation pneumonitis;
- •Symptoms of active central nervous system metastases;
- •History of allergy to recombinant humanized or chimeric antibodies, or allergy to any excipient of Lutetium [177Lu] BL-ARC001;
- •Previous organ transplantation or allogeneic hematopoietic stem cell transplantation;
- •Cumulative dose of anthracyclines > 360 mg/m² in previous (neo)adjuvant anthracycline therapy;
- •Positive human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •Active infection requiring systemic treatment;
- •Participation in another clinical trial within 4 weeks prior to the first dose;
- •Pregnant or lactating women;
- •Any other condition deemed by the investigator as unsuitable for participation in this clinical trial.
研究组 & 干预措施
Lutetium [177Lu] BL-ARC001
Participants receive Lutetium [177Lu] BL-ARC001 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: Lutetium [177Lu] BL-ARC001 (Drug)
结局指标
主要结局
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 Lutetium \[177Lu\] BL-ARC001.
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.
次要结局
- Cmax(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- Radiation Characteristics(Up to approximately 24 months)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- CL (Clearance)(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)
- ADA (anti-drug antibody)(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
- Distribution Characteristics(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- Phase Ib: Duration of Response (DOR)(Up to approximately 24 months)