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 Gastrointestinal Tumors and Other Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 45
- 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, multicenter, dose-escalation and expanded-enrollment, nonrandomized 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 gastrointestinal tumors 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 and follow the requirements of the protocol;
- •No gender limit;
- •Age: ≥18 years old and ≤75 years old (phase Ia); ≥18 years old (phase Ib);
- •Expected survival time ≥3 months;
- •Pathologically and/or cytologically confirmed locally advanced or metastatic gastrointestinal tumors and other solid tumors that failed standard treatment;
- •Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 2 years;
- •Must have at least one measurable lesion according to RECIST v1.1 definition;
- •ECOG 0 or 1;
- •Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
- •Organ function level must meet the requirements;
- •Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;
- •Urine protein ≤2+ or ≤1000mg/24h;
- •For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, and must be non-lactating; All enrolled patients (regardless of male or female) should use adequate barrier contraception during the whole treatment cycle and for 6 months after the end of treatment;
- •Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.
排除标准
- •Anti-tumor therapy such as chemotherapy or biological therapy has been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;
- •History of severe heart disease;
- •QT prolongation, complete left bundle branch block, III degree atrioventricular block;
- •Active autoimmune and inflammatory diseases;
- •Other malignant tumors diagnosed within 5 years before the first dose;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months before the first dose;
- •Poorly controlled hypertension;
- •Patients with poor glycemic control;
- •History of ILD requiring steroid therapy, or current ILD or ≥ grade 2 radiation pneumonitis;
- •Complicated pulmonary diseases leading to clinically severe respiratory function impairment;
- •Symptoms of active central nervous system metastasis;
- •Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of the ingredients of BL-M09D1;
- •Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
- •Anthracycline cumulative dose > 360 mg/m2 in previous (new) adjuvant therapy;
- •HIV antibody positive, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •Active infection requiring systemic therapy within 4 weeks before the first dose of study drug; Signs of pulmonary infection or active pulmonary inflammation within 2 weeks before the first dose;
- •Pleural, abdominal, pelvic or pericardial effusion requiring drainage and/or with symptoms within 4 weeks before the first dose of study drug;
- •Use of another clinical trial within 4 weeks or 5 half-lives before the first dose;
- •Pregnant or lactating women;
- •Other conditions for participation in the trial were not considered appropriate by the investigator.
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
- Cmax(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- T1/2(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)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- AUC0-t(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)