A Phase IIa/IIb Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-M09D1 for Injection in Patients With Locally Advanced or Metastatic Urothelial Carcinoma and Other Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Phase IIa: Recommended Phase II Dose (RP2D)
研究概览
简要总结
This study is a single-arm, open-label, multicenter, non-randomized phase IIa/IIb clinical study to evaluate the efficacy and safety of BL-M09D1 for injection in patients with locally advanced or metastatic urothelial carcinoma 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 75 Years（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;
- •Age: ≥18 years and ≤75 years;
- •Expected survival time ≥3 months;
- •Locally advanced or metastatic urothelial carcinoma and other solid tumors;
- •Agree to provide archived tumor tissue specimens or fresh tissue samples from the primary or metastatic lesion within 2 years;
- •Must have at least one measurable lesion as defined by RECIST v1.1;
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- •Toxicity from prior antitumor therapy has recovered to ≤Grade 1 as defined by NCI-CTCAE v6.0;
- •No severe cardiac dysfunction, with 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;
- •For premenopausal female trial participants of childbearing potential, a serum pregnancy test must be performed within 7 days before the start of treatment. The serum pregnancy test must exclude pregnancy, and the participant must not be breastfeeding; all enrolled trial participants and their partners must agree to use adequate highly effective contraceptive measures throughout the entire treatment period and for 7 months (women) and 4 months (men) after the end of treatment. It is recommended to also use other contraceptive methods, such as barrier contraception;
- •Trial participants are able and willing to comply with the visits, treatment plans, laboratory tests, and other study-related procedures specified in the study protocol.
排除标准
- •Received chemotherapy, targeted therapy, biological therapy, etc. within 4 weeks or 5 half-lives before the first dose;
- •History of severe heart disease;
- •Prolonged QT interval, complete left bundle branch block, third-degree atrioventricular block; frequent and uncontrollable arrhythmias;
- •Active autoimmune disease or inflammatory disease;
- •Diagnosed with other malignancies within 5 years before the first dose;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months before the first dose;
- •Hypertension poorly controlled by two antihypertensive drugs;
- •Patients with poorly controlled blood glucose;
- •History of interstitial lung disease requiring hormone therapy, or current ILD or grade >= 2 radiation pneumonitis;
- •Concurrent lung disease causing clinically severe impairment of respiratory function;
- •Active central nervous system metastasis;
- •Patients with a history of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient of BL-M09D1;
- •Previous organ transplantation or allogeneic hematopoietic stem cell transplantation;
- •Positive human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •Active infection requiring systemic treatment within 4 weeks before the first study drug administration;
- •Pleural, abdominal, pelvic effusion, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks before the first study drug administration;
- •Participated in another clinical trial within 4 weeks or 5 half-lives before the first dose;
- •Trial participants with clinically significant bleeding or a clear bleeding tendency within 4 weeks before the first study drug administration;
- •Inflammatory bowel disease with symptoms or requiring drug intervention, or partial or complete intestinal obstruction, within 4 weeks before the first study drug administration;
- •Known mental illness or disorder that may affect trial compliance;
- •Trial participants planning to receive vaccination or who received a live vaccine within 28 days before the first dose;
- •Pregnant or breastfeeding women;
- •Other circumstances in which the investigator considers the patient unsuitable for participation in this clinical trial.
研究组 & 干预措施
BL-M09D1
Participants receive BL-M09D1 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 IIa: 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.
Phase IIa: Treatment-Emergent Adverse Event (TEAE)
时间窗: Up to approximately 24 months
TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-M09D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M09D1.
Phase IIb: Objective Response Rate (ORR)
时间窗: Up to approximately 24 months
Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS).
次要结局
- Phase IIa: Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase IIa/IIb: Progression-free Survival (PFS)(Up to approximately 24 months)
- Phase IIa/IIb: Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase IIa/IIb: Duration of Response (DOR)(Up to approximately 24 months)
- Phase IIb: Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
- Anti-drug Antibody (ADA)(Up to approximately 24 months)
- Neutralizing Antibody(NAb)(Up to approximately 24 months)