A Single-Arm, Open-Label, Compassionate Use Study of VSV-02 Administered Intravenously and Intratumorally in Patients With Advanced Solid Tumors

1. 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.

Performance Status: ECOG score of 0-2 and life expectancy ≥ 12 weeks. Organ Function: Adequate hematological, hepatic, and renal function. Key exclusion criteria include: symptomatic or untreated brain metastases (asymptomatic, stable for ≥3 months post-treatment allowed); active autoimmune disease; significant cardiovascular disease; active infection; concurrent anticoagulant therapy; and requirement for high-dose systemic corticosteroids. 5. Interventions Participants will receive VSV-02 Injection (supplied by Shanghai Rongrui Pharmaceutical Technology Co., Ltd.; specification: 1mL/vial; titer: 3.0×10^10 PFU/mL) on Day 1 of each 21-day cycle for up to 6 cycles. Dosing involves concurrent IV and IT administration. The starting dose level is 6×10^10 PFU (IT) + 6×10^11 PFU (IV). The IT injection volume will be determined based on tumor size measured within 24 hours prior to injection, with a maximum total volume of 10 mL per subject per day. Treatment continues until disease progression (with clinical deterioration), unacceptable toxicity, withdrawal of consent, completion of 6 cycles, or other protocol-specified criteria. 6. Outcome Measures Efficacy Assessments: Tumor assessments will be performed per RECIST 1.1. Subjects with initial radiographic progression per RECIST 1.1 but without clinical deterioration may continue treatment, with progression confirmed per iRECIST ≥4 weeks later. Primary efficacy endpoints are ORR, DCR, DoR, PFS, and OS.

Safety Assessments: Safety will be monitored throughout the study. AEs will be graded according to NCI CTCAE v5.0. Assessments include monitoring of AEs/SAEs, DLTs/MTD, clinical laboratory tests, vital signs, ECGs, and physical examinations.