A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M24D1 for 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
- 33
- 试验地点
- 1
- 主要终点
- Phase Ia: Maximum tolerated dose (MTD)
研究概览
简要总结
This study is an open, multicenter, non-randomized phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M24D1 for Injection in patients with locally advanced or metastatic gastrointestinal tumors and other 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;
- •No gender restrictions;
- •Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib);
- •Expected survival time ≥3 months;
- •Locally advanced or metastatic digestive tract tumors and other 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 treatments 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 (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
- •Urine protein ≤2+ or ≤1000mg/24h;
- •For premenopausal women with childbearing potential, a pregnancy test must be conducted within 7 days before starting treatment, serum pregnancy must be negative, and they must not be breastfeeding; all enrolled patients (regardless of gender) should adopt adequate barrier contraception throughout the treatment cycle and for 6 months after treatment ends.
排除标准
- •Use of chemotherapy, biological therapy, or immunotherapy within 4 weeks prior to the first dose or within 5 half-lives;
- •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;
- •Patients with poorly controlled blood glucose;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose;
- •Lung diseases graded ≥3 according to CTCAE v5.0;
- •Symptoms of active central nervous system metastases;
- •History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of BL-M24D1;
- •Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
- •Cumulative dose of anthracyclines >360 mg/m² in previous (neo)adjuvant anthracycline therapy;
- •Human immunodeficiency virus antibody positivity, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •History of interstitial lung disease (ILD) requiring steroid treatment, or current ILD;
- •Active infection requiring systemic treatment within 4 weeks prior to the first investigational drug dose;
- •Pleural, abdominal, pelvic, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first investigational drug dose;
- •Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to the first investigational drug dose;
- •Participation in another clinical trial within 4 weeks prior to the first dose;
- •Pregnant or lactating women;
- •Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.
研究组 & 干预措施
BL-M24D1
Participants receive BL-M24D1 as intravenous infusion for the first cycle (2 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-M24D1 (Drug)
结局指标
主要结局
Phase Ia: Maximum tolerated dose (MTD)
时间窗: Up to 28 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 Ia: Dose limiting toxicity (DLT)
时间窗: Up to 28 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 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-M24D1.
次要结局
- ADA (anti-drug antibody)(Up to approximately 24 months)
- 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)
- 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)