Phase I Clinical Study on the Safety, Tolerability, and Pharmacokinetics of Recombinant Human nsIL12 Oncolytic Adenovirus Injection (BioTTT001) in Patients With Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This is a Phase 1 open-label study to evaluate the safety, tolerability, and pharmacokinetics of Recombinant Human nsIL12 Oncolytic Adenovirus Injection (BioTTT001) at dose of 5×10∧9VP、5×10∧10VP、5×10∧11VP in Patients With Malignant Solid Tumors. Subjects will be treated with a single dose of BioTTT001 Injection after the screening period.
详细描述
This study is a single arm, open label, single center dose escalation trial. Three study drug dosage groups are pre-set, namely 5 × 10∧9VP、5 × 10∧10VP、 5 × 10∧11VP. According to the principle of dose escalation from low to high, the "3+3" dose escalation method is adopted. In theory, in order to protect the safety of the subjects, during the DLT observation phase of the same dose group, the first subject in each dose group can only be enrolled in the second subject after at least 2 weeks after administration. The DLT observation period for each subject is 28 days after the first administration, and the last subject in each dose group can only enter the next dose escalation after completing the DLT observation period. At least 3 subjects are enrolled in each dose group, and each subject only receives one corresponding dose.
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
- •Age range from 18 to 80 years old (including the threshold), no gender restrictions.
- •Patients with histologically and/or cytologically confirmed malignant solid tumors, who have experienced at least one-line standard treatment failure or intolerance, or lack standard treatment options. Focus on malignancies in the head and neck, colorectal cancer, skin malignancies, and cervical cancer.
- •At least one assessable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.
- •Assessed by the investigators to have lesions suitable for intratumoral injection (assessable lesions and intratumoral injection lesions can refer to the same lesion).
排除标准
- •Known allergy to the investigational drug or its components.
- •Previous treatment with other adenovirus drugs.
- •Patients with active autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, etc.), except type 1 diabetes, hypothyroidism that only needs hormone replacement therapy, and skin diseases that do not need systemic treatment (such as vitiligo, psoriasis or alopecia).
- •Patients who have not recovered from the adverse reactions of previous treatments (the treatment-related toxicity ≤ grade 2, except for alopecia, pigmentation or other tolerable events judged by the investigator ).
研究组 & 干预措施
BioTTT001 injection
BioTTT001 is administered as a single Intratumoral injection. The dose groups to be infusion were 5×10^9 viral particle (VP) ,5×10^10 VP and 5×10^11 VP based on the 3+3 dose escalation principle.
干预措施: BioTTT001 injection (Biological)
结局指标
主要结局
Incidence of adverse events
时间窗: 28 days within BioTTT001 injection
The incidence and severity of all types of adverse events evaluated based on NCI-CTCAE V5.0 assessment
MTD
时间窗: 28 days within BioTTT001 injection
Maximum tolerated dose (MTD)
次要结局
- Serum neutralizing antibody level(28 days within BioTTT001 injection)
- Plasma Adenovirus (ADV) copies(28 days within BioTTT001 injection)
- ORR(From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- DCR(From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- PFS(From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- ADV copies in various sites(28 days within BioTTT001 injection)
- Serum interleukin-12 (IL-12) level(28 days within BioTTT001 injection)