An Open-Label, Dose Escalation Study of the Safety and Tolerability of Oncolytic Virus Injection(RT-01) When Administered Via Intratumoral Injection in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicities (DLT)
研究概览
简要总结
This is an open-label, dose escalation study of the safety and tolerability of oncolytic virus injection(RT-01) when administered via intratumoral injection in patients with advanced solid tumors. The purpose of this study is to assess the safety and tolerability of RT-01 and to determine the recommended phase 2 dose (RP2D) for further study. The study will also evaluate antitumor activity, objective response rate, pharmacokinetics and virus shedding of RT-01.
详细描述
This is an investigator initiated , open-label, study of RT-01 given via intratumoral (IT) injection as a single agent in participants with advanced solid tumors. The study is a single agent dose escalation which will use a 3+3 design to evaluate escalating doses of RT-01. Total enrollment will depend on the toxicities and/or activity observed, with approximately 7-18 evaluable participants enrolled.
The primary study objective is to determine the safety, tolerability, and maximum tolerated dose (MTD) of intratumoral administration of RT-01 as a single agent. Secondary objectives will assess efficacy overall response rate, as well as disease control rate, progression free survival, duration of response, and anti-tumor immune responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Male or female aged ≥ 18 years;
- •Subjects must have histologically- or cytologically-confirmed diagnosis of advanced solid tumor(s) and have progressed on or is not eligible for available standard therapy;
- •Subjects have At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (non-nodal lesions with longest diameter ≥ 10 mm, or nodal lesions with short diameter ≥ 15 mm);
- •ECOG score of 0 ~ 2;
- •Adequate bone marrow, hepatic and renal and coagulation function;
- •Women of childbearing age who have a negative pregnancy test within 7 days before treatment. Female patients of childbearing age, and male patients with partners of childbearing age must agree to use at least one medically recognized contraceptive method during study treatment and within at least 6 months after the last dose of investigational drug;
- •Voluntarily participated in this study, signed the informed consent form, had good compliance, and cooperated with the follow-up.
排除标准
- •Subjects with known brain metastasis and/or clinically history tumor brain of metastasis；
- •Subjects who have received anti-tumor therapy such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, etc within 4 weeks；
- •Subjects who have participate in another interventional study while receiving study IP within 4 weeks；
- •Subjects who have had major surgery ≤ 4 weeks of dosing；
- •Patients in any condition requiring systemic treatment with corticosteroids (prednisone > 10 mg/day or equivalent of the similar drug) or other immunosuppressive agents within 14 days prior to investigational drug administration, but currently or previously treated with any of the following steroid regimens, were included:
- •Topical, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids with minimal systemic absorption;
- •Prophylactic short-term (≤ 7 days) use of corticosteroids (e.g., allergy to contrast media) or for the treatment of non-autoimmune diseases (e.g., delayed hypersensitivity caused by contact allergens)
- •Subjects received live vaccines within 7 days of initiation of study treatment；
- •Subjects with adverse reactions caused by previous anti-tumor treatment not recovered to (CTCAE 5.0) grade 1 (except alopecia)；
- •Subjects who have any active infection；
- •Subjects with known positive history of human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS)；
- •Subjects who have active hepatitis；
- •Subjects who have serious cardiovascular system disorders history；
- •Subjects with active autoimmune diseases or history of autoimmune diseases that may relapse；
- •Subjects having any serious uncontrolled disease or in other conditions that would preclude them from receiving study treatment and are considered unsuitable for this study in the opinion of the investigator.
- •Subjects in other conditions that are considered unsuitable for this study by the investigator.
研究组 & 干预措施
Oncolytic virus injection(RT-01) for patients with advanced solid tumors
Intratumoral administration of RT-01 as single agent for patients with advanced solid tumors.The injection dose of RT-01 was determined by the lesion size:
- mL for lesion length <1.5 cm;
- mL for lesion length between 1.5 cm and 2.5 cm;
- mL for lesion length between 2.5 cm and 5.0 cm;
- mL for lesion length between >5 cm
干预措施: Oncolytic Virus Injection(RT-01) (Biological)
结局指标
主要结局
Dose Limiting Toxicities (DLT)
时间窗: Up to 28 days
To define the maximum tolerated dose (MTD) of intratumoral administration of RT-01 injection in humans with malignant tumors.
次要结局
- Safety and tolerability assessed by Adverse Events (AEs)(Up to 6 months)
- Number of participants with laboratory value abnormalities and/or adverse events(Up to 6 months)
- Number of participants with vital sign abnormalities and /or adverse event(Up to 6 months)
- Safety assessed by 12- lead electrocardiograms (ECGs) adverse events(Up to 6 months)
- To evaluate the efficacy assessed per RECIST and iRECIST(Up to 2 years form first dose of RT-01)
- Number of Participants With Response(at baseline, 2, 4, 7, 14, 28 days after injection)
- Viral shedding of RT-01 in blood(Up to 6 months)
- Presence of neutralizing antibodies of antidrug antibodies (ADAs) development(Up to 6 months)