A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M09D1 for Injection in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer and Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 31
- 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 cohort-expansion, non-randomized Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of BL-M09D1 for injection in patients with locally advanced or metastatic non-small cell lung cancer and other solid tumors.
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;
- •Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer or other solid tumors that have failed standard treatment;
- •Willing to provide archived or fresh tumor tissue samples from primary or metastatic lesions within the past 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 have recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%;
- •Organ function levels must meet the 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 ≤1000mg/24h;
- •For premenopausal women with childbearing potential, a serum pregnancy test must be negative within 7 days before starting treatment, and they must not be breastfeeding. All enrolled patients (regardless of gender) must use adequate barrier contraception throughout the treatment period and for 6 months after treatment completion;
- •The subject has the ability and willingness to comply with the visits, treatment plans, laboratory tests, and other study-related procedures specified in the protocol.
排除标准
- •Received chemotherapy, biological therapy, immunotherapy, etc., within 4 weeks or 5 half-lives before the first dose;
- •History of severe cardiac disease;
- •Prolonged QT interval, complete left bundle branch block, or third-degree atrioventricular block;
- •Active autoimmune or inflammatory diseases;
- •Diagnosed with another malignancy within 5 years before the first dose (except cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix);
- •Unstable thrombotic events requiring therapeutic intervention within 6 months before the first dose;
- •Poorly controlled hypertension;
- •Poorly controlled diabetes mellitus;
- •History of interstitial lung disease (ILD) requiring steroid therapy, current ILD, or ≥Grade 2 radiation pneumonitis;
- •Concurrent pulmonary diseases resulting in clinically severe respiratory impairment;
- •Active central nervous system metastases;
- •History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or hypersensitivity to any excipient of BL-M09D1;
- •Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
- •Cumulative dose of anthracyclines >360 mg/m² in prior (neo)adjuvant anthracycline therapy;
- •Positive for human immunodeficiency virus (HIV) antibody, active tuberculosis, active hepatitis B virus (HBV) infection, or active hepatitis C virus (HCV) infection;
- •Active infections requiring systemic treatment within 4 weeks before the first study drug administration;
- •Pleural, peritoneal, pelvic, or pericardial effusion requiring drainage and/or symptomatic within 4 weeks before the first study drug administration;
- •Participation in another clinical trial within 4 weeks or 5 half-lives before 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-M09D1
Participants receive BL-M09D1 as intravenous infusion 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: BL-M09D1 (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 BL-M09D1.
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)
- 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)