NCT04758897Unknown1 期
A Dose Ascending, Open Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics Characteristics of VG161 in Subjects With Advanced Malignant Solid Tumors
CNBG-Virogin Biotech (Shanghai) Ltd.2 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2021年4月14日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Occurence of DLT
研究概览
简要总结
VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This Phase I study will be conducted in HSV-seropositive subjects with advanced malignant solid tumors that are refractory to conventional therapies. This is an open label study to determine the safety and tolerability of VG161, and recommended dose of VG161 for Phase II trials.
详细描述
The trial will be conducted in 7 dose ascending cohorts, including 3 single dose accelerated titration design pilots and 4 multiple dose escalation groups.
Descriptive statistics will be used to summarize all data.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females aged within 18 to 80 years.
- •Subject with late stage carcinoma which is refractory/relapsed after and/or intolerant of standard therapies or for which no standard therapy exists.
- •There is at lease one injectable tumor lesion that meet the requirements of the assigned dose level. The superficial lesions are preferred, and the deep lesions that can be injected under the guidance of B ultrasound or computed tomography (CT) scan can also be selected.
- •Eastern Cooperative Oncology Group (ECOG) scores 0 or
- •Life expectancy is at least 3 months.
- •Required organ function:
- •Hematology blood (no blood transfusion or colony stimulating factor treatment within 14 days): Absolute neutrophil count (ANC)≥1.5×10^9L, Platelets ( PLT)≥75×10^9L, hemoglobin (Hb)≥85g/L; 2) Liver function: Total Serum bilirubin (TBIL)≤1.5×ULN (the upper limit of the reference range), Alanine aminotransferase (ALT)≤3×ULN, aspartate aminotransferase (AST)≤3×ULN (acceptable for patients with liver metastasis or liver cancer: TBIL≤5×ULN, AST≤5×ULN, ALT≤5×ULN); 3) Renal function: Serum creatinine≤1.5×ULN, and creatinine clearance≥50 ml/min (calculated per Cockcroft-Gault formula); 4) Coagulation function: activated partial thromboplastin time (APTT)≤1.5×ULN, international standardized ratio (INR)≤1.5×ULN.
- •Subjects of childbearing potential (male and female) must agree to use a reliable contraceptive method (hormone or barrier method or abstinence) during the study and for at least 90 days following the last dose; females of childbearing potential must have a negative blood or urine pregnancy test within 7 days of study enrollment.
- •Signed written informed consent.
排除标准
- •Subject in prior anti-tumor therapies such as chemotherapy, radiotherapy, biotherapy, endocrinotherapy, targeted therapy, immunotherapy within 4 weeks of study treatment initiation.
- •Participation in clinical trials of any other investigational agents within 4 weeks of study treatment initiation.
- •Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks of study treatment initiation.
- •Patients who received systemic treatment with either corticosteroids ( >10 mg/ daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study treatment initiation.
- •Subjects with any ≥Grade 1 toxicity (as per NCI CTC AE Version 5.0) related to prior anti-cancer therapy (except for toxicity that the investigator assessed to be no safety risk, such as alopecia.).
- •Subjects with any uncontrolled active Central Nervous System (CNS) metastasis or meningeal metastasis with clinical symptoms.
- •Seronegative for Herpes Simplex Virus (HSV) (HSV-1IgG and HSV-1IgM).
- •Subjects with the relapse of HSV infection and relevant clinical manifestations, such as lip herpes, herpes keratitis, herpes dermatitis, and genital herpes.
- •Subjects with other uncontrolled active infections.
- •Known history of immunodeficiency and test positive of human immunodeficiency virus (HIV).
- •Active infection of hepatitis B (HBV) (hepatitis b virus titer higher than the detection limit or those requiring antiviral therapy), or hepatitis C virus (HCV).
- •History of severe cardiovascular disease:
- •Ventricular arrhythmias requiring clinical intervention; 2)QTc interval >480 ms; 3)Acute coronary syndrome, congestive heart failure, stroke or other cardiovascular events of III grade or above within 6 months; 4)The cardiac function grade≥II or left ventricular ejection fraction (LVEF) <50% per the New York Heart Association (NYA); 5)Uncontrolled hypertension.
- •Subjects with active or past autoimmune diseases that are likely to recur (e.g. systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.); acceptable for patients with clinically stable autoimmune thyroiditis.
- •Subjects with any prior ≥Grade 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent.
- •known to have alcohol or drug dependence.
- •Persons with mental disorders or poor compliance.
- •Pregnant or lactating women.
- •Subjects with any significant unrelated systemic illness that to the investigator's opinion would compromise the subject's eligibility to participate the study.
研究组 & 干预措施
Single Arm
Experimental
- 5.0*10^7 on D1
- 1.0*10^8 on D1
- 2.0*10^8 on D1
- 2.0*10^8 on D1 and D2
- 2.0*10^8 on Days 1 to 3
- 2.0*10^8 on Days 1 to 4
- 2.0*10^8 on Days 1 to 5
干预措施: Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell)) (Drug)
结局指标
主要结局
Occurence of DLT
时间窗: 1 month
Occurence of DLT (Dose Limiting Toxicity)
MTD/RP2D
时间窗: 1 month
MTD (Maximum tolerable dose) / RP2D (Recommended dose for phase II)
Occurence of AE and SAE（NCI CTCAE 5.0）
时间窗: 7 months
Occurence of Adverse Event (AE) and Serious Adverse Event (SAE) （NCI CTCAE 5.0）
Frequency of AE and SAE（NCI CTCAE 5.0）
时间窗: 7 months
Frequency of Adverse Event (AE) and Serious Adverse Event (SAE) （NCI CTCAE 5.0）
Numbers of DLT
时间窗: 1 month
Numbers of DLT (Dose Limiting Toxicity)
次要结局
- CD3+, CD4+, CD8+(7 months)
- IL15(7 months)
- DCR(7 months)
- Tmax(h)(At the end of Cycle 1 (each cycle is 28 days))
- mPFS(7 months)
- Cmax(copies/ugDNA)(At the end of Cycle 1 (each cycle is 28 days))
- ORR(7 months)
- PD-L1, PD-1(7 months)
- Existence of Biomarkers(4 months)
研究者
研究点 (2)
Loading locations...
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