A Single-Arm, Open-Label, Compassionate Use Study of VSV-02 Administered Intravenously and Intratumorally in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This is a clinical study for patients with advanced solid tumors who have limited or no effective treatment options available. The study aims to evaluate a new investigational drug called VSV-02 Injection, which is developed by Shanghai Rongrui Pharmaceutical Technology Co., Ltd.
The main purpose of this open-label, single-arm study is to assess the preliminary effectiveness and safety of VSV-02 when it is given through two routes: directly into a vein (intravenously) and by injection directly into the tumor (intratumorally). Patients will receive the treatment on the first day of each 3-week cycle, for up to 6 cycles.
The study will follow a dose-escalation design to find a suitable dose. Treatment may be stopped if the disease progresses, if side effects become intolerable, or if the patient chooses to withdraw, among other reasons. Researchers will closely monitor patients to see if VSV-02 can help control the cancer and to record any side effects that may occur.
详细描述
- Background Cancer remains a major public health concern worldwide. Despite advances in multimodal therapies including surgery, chemotherapy, radiotherapy, and targeted agents, effective treatments for recurrent or metastatic solid tumors are still limited. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1, has revolutionized oncology, but primary and acquired resistance remain significant challenges.
Oncolytic viruses (OVs) represent a promising strategy to enhance antitumor immunity and overcome resistance. VSV-02 is an attenuated Vesicular Stomatitis Virus engineered to encode a CD3/PD-L1 bispecific antibody. It selectively infects and lyses tumor cells (oncolysis) and locally expresses the bispecific antibody, which bridges T cells and PD-L1-positive tumor cells to force T-cell activation and counteract PD-1/PD-L1-mediated suppression. This dual mechanism of action aims to stimulate a potent, localized immune response, making VSV-02 a compelling candidate for cancer immunotherapy. 2. Objectives Primary Objectives: To evaluate the preliminary efficacy of VSV-02 Injection administered via intravenous (IV) and intratumoral (IT) routes in subjects with advanced solid tumors, as measured by Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DoR), Progression-Free Survival (PFS), and Overall Survival (OS) per RECIST 1.1.
Secondary Objectives: To assess the safety and tolerability profile of VSV-02 (IV and IT), including the incidence and characteristics of adverse events (AEs), and changes in laboratory parameters, vital signs, ECGs, and physical examinations. 3. Study Design Trial Phase: Phase I Intervention Model: Single Group Assignment Allocation: Non-Randomized Masking: None (Open-Label) Primary Purpose: Treatment This is a single-arm, open-label, dose-escalation study. The study will follow a standard "3+3" design to evaluate the safety and preliminary efficacy of VSV-02. 4. Eligibility Criteria Age: ≥ 18 years. Diagnosis: Histologically or cytologically confirmed advanced solid tumors (e.g., melanoma, head and neck squamous cell carcinoma, cervical cancer, osteosarcoma, nasopharyngeal carcinoma, breast cancer, lung cancer, colorectal cancer, liver cancer, gastric cancer).
Prior Therapy: Disease progression after at least two prior standard systemic therapies (including targeted therapy, where applicable), or for whom no standard therapy exists. Specific requirements vary by tumor type.
Measurable Disease: At least one measurable lesion per RECIST 1.1 and at least one lesion accessible for IT injection.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary signed informed consent.
- •Age ≥ 18 years.
- •Histologically or cytologically confirmed advanced solid tumor (e.g., melanoma, head and neck squamous cell carcinoma, cervical cancer, osteosarcoma, nasopharyngeal carcinoma, breast cancer, lung cancer, colorectal cancer, liver cancer, gastric cancer).
- •Disease progression after at least two prior lines of standard therapy (including targeted therapy), or for whom no standard therapy exists or is medically unsuitable.
- •At least one measurable lesion per RECIST 1.1 criteria.
- •At least one lesion accessible for intratumoral injection.
- •ECOG performance status of 0-
- •Life expectancy ≥ 12 weeks.
- •Adequate organ and bone marrow function.
- •Negative pregnancy test for women of childbearing potential.
- •Agreement to use effective contraception during the study and for at least 6 months after the last dose.
排除标准
- •Symptomatic or untreated brain metastases (asymptomatic or stable for ≥3 months after local therapy allowed).
- •Radiotherapy to the target lesion within 2 months.
- •History of other active malignancy within 5 years (with specific exceptions).
- •Lesion intended for injection with a longest diameter > 100 mm.
- •Participation in another interventional clinical trial within 4 weeks.
- •Prior or planned organ/tissue transplantation.
- •Active HIV, Hepatitis B, Hepatitis C, or Syphilis infection meeting specific criteria.
- •Requirement for concomitant antiviral or therapeutic anticoagulation.
- •Uncontrolled ≥ Grade 3 active infection.
- •Specific washout periods for prior anti-cancer therapies not met.
- •Uncontrolled cardiovascular disease.
- •Active or history of autoimmune disease (with specific exceptions).
- •Requirement for systemic corticosteroids (>10 mg prednisone equivalent) within 14 days or during the study.
- •Tumors located in high-risk anatomical sites.
- •Administration of live vaccines during the study period.
- •Known hypersensitivity to any component of the study drug or related immunotherapies.
- •History of severe mental illness, substance abuse, or other conditions that may interfere with study compliance.
- •Pregnancy or lactation.
- •Toxicities from previous anti-cancer therapy not recovered to ≤ Grade 1 (except alopecia).
- •Any other condition deemed inappropriate for participation by the investigator.
研究组 & 干预措施
VSV-02 Dose Escalation Group
Participants will receive VSV-02 via intravenous (IV) and intratumoral (IT) injection in a dose-escalation manner. The starting dose is 6×10^10 PFU (IT) + 6×10^11 PFU (IV). Dosing occurs on Day 1 of each 21-day cycle for up to 6 cycles.
干预措施: VSV-02 Injection (Biological)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: From enrollment until the first occurrence of disease progression or the end of treatment, up to 24 months.
ORR is defined as the proportion of participants achieving a best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as assessed by the investigator.
Disease Control Rate (DCR)
时间窗: From enrollment until the first occurrence of disease progression or the end of treatment, up to 24 months.
DCR is defined as the proportion of participants achieving a best overall response of complete response (CR), partial response (PR), or stable disease (SD) (lasting for at least 6 weeks) per RECIST 1.1.
Duration of Response (DoR)
时间窗: From the first objective response (CR or PR) until disease progression or death from any cause, assessed up to 36 months.
DoR is defined as the time from the first documentation of CR or PR to the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first, as per RECIST 1.1.
Progression-Free Survival (PFS)
时间窗: From enrollment until the first occurrence of disease progression or death from any cause, assessed up to 36 months.
PFS is defined as the time from enrollment to the first documentation of progressive disease (PD) as per RECIST 1.1 or death from any cause, whichever occurs first.
verall Survival (OS)
时间窗: From enrollment until death from any cause, assessed up to 60 months.
OS is defined as the time from enrollment to death due to any cause.
次要结局
- Incidence of Adverse Events (AEs)(From first dose of study drug until 30 days after the last dose, up to 7 months.)