A Phase 1, Multicenter, Open-label, Dose-increasing Study to Evaluate the Safety, Tolerability, PK/PD and Preliminary Efficacy of Y101D, a Recombinant Anti-PD-L1 and TGF-β Bispecific Antibody for Injection, in Patients With Metastatic or Locally Advanced Solid Tumors

Wuhan YZY Biopharma Co., Ltd.3 个研究点分布在 1 个国家目标入组 50 人开始时间: 2021年8月6日最近更新: 2025年7月20日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Wuhan YZY Biopharma Co., Ltd.
入组人数: 50
试验地点: 3
主要终点: Adverse Events according to CTCAE V5.0

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a phase 1, multicenter, open-label study to evaluate the safety, tolerability, PK, PD, immunogenicity and preliminary efficacy of Y101D in patients with metastatic or locally advanced solid tumors.

详细描述

This study will consist of two parts: dose escalation part and cohort expansion part.

In dose escalation part, up to 5 dose-escalation cohorts will be sequentially enrolled in this study. The five dose levels are 1, 3, 10, 20 and 30 mg/kg. DLTs will be evaluated during the first treatment cycle, which is 28 days. The study consists of a 4-week screening period, a 4-week core treatment period for DLT evaluation, a treatment extension period, a safety follow-up visit for approximately 30 days following the last dose of Y101D, and survival follow-ups every 3 months thereafter.

In cohort expansion part, To further characterize safety and efficacy of Y101D, cohort expansion will be allowed in the following two circumstances: MTD cohort expansion if the MTD could be identified; Benefited dose cohort if it could be determined by Investigator.

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

•Age 18~75 (including 18 and 75 years old), gender is not limited;
•Pathologically confirmed metastatic or locally advanced solid tumors with failure or absence of standard care;
•ECOG physical status score must be 0~1;
•Expected survival of subjects evaluated by the investigator ≥3 months;
•Hemogram: absolute neutrophil count (ANC) ≥1.5×109/L, hemoglobin ≥90g/L (no red blood cells were injected within 14 days before the first administration), platelet ≥90×109/L;
•Liver: bilirubin ≤1.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal value;If the subject has liver metastasis, ALT and AST are allowed to be less than 5 times the upper limit of normal value;
•Kidney: Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance ≥ 60 mL/min (using standard Cockcroft-Gault formula);
•Understand and voluntarily sign written informed consent.

排除标准

•Have received chemotherapy, radiotherapy (local palliative radiotherapy for 14 days) and immunotherapy within 28 days before the first administration, and have received small molecule targeted drugs or Chinese patent drugs with anti-tumor indications within 14 days;
•Major surgery (except diagnostic biopsy) within 28 days prior to the first dose;
•Subjects with central nervous system (CNS) metastases causing clinical symptoms or requiring therapeutic intervention;Patients who had previously received BMs were included if they were asymptomatic ≥4 weeks prior to initial dosing, had stable disease on radiographic findings, and did not require corticosteroid or anticonvulsant therapy;
•Receive any organ transplantation, including allogeneic stem cell transplantation, except those that do not require immunosuppression (e.g. cornea transplantation, hair transplantation);
•Adverse events caused by previous antitumor therapy have not recovered (i.e., grade 1 or at baseline), except for hair loss and grade 2 neuropathy, hormone replacement hypothyroidism, or other confirmed chronic adverse events;
•Subjects with a history of malignancy (non-study tumor) within 3 years prior to the first study administration date (other than skin squamous cell carcinoma and basal cell carcinoma, carcinoma in situ of the cervix or breast, or other non-invasive lesions that the Investigator and Sponsor agree have been cured and have a very low risk of recurrence within 3 years);
•Have a known allergy, hypersensitivity or intolerance to corticosteroids, monoclonal antibodies or human proteins or their excipients;
•Uncontrolled active infection (CTCAE≥2);
•Subjects with severe respiratory diseases judged by the researcher to be unsuitable for inclusion;
•Subjects with a history of serious cardiovascular disease, including previous coronary artery bypass grafting or stent implantation, myocardial infarction or cerebrovascular accident within 6 months, history of congestive heart failure or unstable angina pectoris, uncontrolled severe hypertension, and arrhythmias requiring medication;
•Active autoimmune diseases (such as inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus (sle), hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, etc.), into the group when the disease is in stable except ZhuangTaiZhe (no need to systemic immune inhibitors to treat symptoms stable under the condition of more than 6 months).
•Subjects with uncontrolled metabolic diseases such as diabetes, severe gastrointestinal bleeding, and severe diarrhea (CTCAE≥2), and subjects with severe gastrointestinal obstruction requiring intervention;
•Human immunodeficiency virus (HIV) antibody positive, hepatitis B virus (HBV) surface antigen positive and HBV DNA test indicated active hepatitis B (HBV-DNA≥1000cps/ml), active hepatitis C (hepatitis C antibody positive and HCV-RNA higher than the detection limit of the analysis method), active syphilis;
•Those who received live (attenuated) virus vaccine within 4 weeks before the first administration;
•Pregnant or lactating women or men or women who have a birth plan within 12 months;
•Have a clear history of neurological or psychiatric disorders, including epilepsy or dementia;
•Subjects with poor compliance or who are considered by the Investigator to be unsuitable for participation in this clinical trial.