Platform Study of VSV-Based Recombinant Oncolytic Viruses for the Treatment of Advanced Malignant Tumors

Official title

A Phase I Platform Study of VSV-Based Recombinant Oncolytic Viruses for the Treatment of Advanced Malignant Tumors

Overview

To evaluate the safety and tolerability of combined administration of VSV injection solutions carrying different targets via multiple routes for treating advanced malignant solid tumors.

Detailed description

This is an open-label, dose-escalation phase I clinical trial designed to evaluate the safety and tolerability of combined administration of vesicular stomatitis virus (VSV) injection solutions carrying different targets via multiple routes in patients with advanced malignant solid tumors, and to preliminarily explore the maximum tolerated dose (MTD), recommended phase II dose (RP2D), as well as the preliminary anti-tumor activity and pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of this regimen.

Interventions

• Biological VSV injection
  Administer twice every two weeks.

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: Within 21 days after administration]
• Incidence of Adverse Events (AEs) [Time frame: From signing ICF until 24 months after the last infusion.]

Secondary outcome measures (8)

• Objective Response Rate (ORR) [Time frame: Imaging assessments will be conducted within 28 days prior to first dose, every 6 weeks (±7 days) during treatment, and every 12 weeks during follow-up until disease progression，up to 24 months.]
• Duration of Response (DOR) [Time frame: Imaging assessments will be conducted within 28 days prior to first dose, every 6 weeks (±7 days) during treatment, and every 12 weeks during follow-up until disease progression，up to 24 months.]
• Progression-Free Survival (PFS) [Time frame: Imaging assessments will be conducted within 28 days prior to first dose, every 6 weeks (±7 days) during treatment, and every 12 weeks during follow-up until disease progression，up to 24 months.]
• Overall Survival (OS) [Time frame: Imaging assessments will be conducted within 28 days prior to first dose, every 6 weeks (±7 days) during treatment, and every 12 weeks during follow-up until disease progression，up to 24 months.]
• Biodistribution and Viral Shedding of VSV [Time frame: Starting before the first dose and continuing until 28 days (±7 days) after the last dose]
• Changes in Peripheral Blood Cytokine Levels [Time frame: Starting before the first dose and continuing until 28 days (±7 days) after the last dose]
• Changes in C-reactive Protein (CRP) Levels [Time frame: Starting before the first dose and continuing until 28 days (±7 days) after the last dose]
• Changes in Peripheral Lymphocyte Subsets [Time frame: Starting before the first dose and continuing until 28 days (±7 days) after the last dose]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the informed consent form, understand this study, and agree to comply with the protocol and complete all trial procedures
• Be at least 18 years of age at the time of signing the ICF, with no gender restrictions.
• Patients with advanced solid tumors confirmed by histopathological/cytological examination of primary and/or metastatic lesions.
• Patients who have failed standard therapy, lack a standard last-line treatment option, or are medically ineligible for standard therapy.
• Subjects with an ECOG performance status of 0-2 and an estimated survival of ≥12 weeks.
• Adequate organ and hematopoietic function: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/LPlatelet count ≥ 75 × 10⁹/L (no platelet transfusion or thrombopoietin (TPO) therapy within 2 weeks prior to first dose)Hemoglobin ≥ 90 g/L (no blood transfusion within 2 weeks)Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CCr) ≥ 50 mL/min Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN for patients with liver metastases, AST and ALT < 5 × ULN， Serum total bilirubin (TBIL) ≤ 2 × ULN， International Normalized Ratio (INR) ≤ 1.5 × ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN
• Women of childbearing potential must have a negative pregnancy test within 7 days prior to treatment initiation.
• Male and female subjects of reproductive potential must agree to use reliable contraception during the trial and for at least 6 months after the last dose. Translated with DeepL.com (free version)

Exclusion criteria

• Subjects with other active malignancies within the past 5 years. Exceptions include subjects who have achieved complete remission and require no follow-up treatment, and subjects with malignancies within the scope of the indication.
• Lesions intended for injection with a maximum diameter >100 mm；
• Subjects who have participated in or are currently participating in other drug or medical device clinical trials within the past 4 weeks；
• Subjects scheduled for or who have previously undergone tissue/organ transplantation；
• Subjects with Human Immunodeficiency Virus (HIV) infection who have experienced AIDS-related opportunistic infections within the past 12 months, or who have a CD4+ T-cell (CD4+) count < 350 cells/uL Patients with positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) at screening, with HBV-DNA above the lower limit of detection patients with positive HCV antibody at screening and HCV-RNA above the lower limit of detection subjects with positive syphilis serology
• Subjects requiring antiviral medication during the study period or within 5 half-lives of antiviral medication at the time of first dosing.
• Subjects requiring therapeutic anticoagulant medication during the study period.
• Subjects with uncontrolled active infection of ≥Grade 3 severity according to CTCAE v5.0 that is clinically significant
• Received antineoplastic therapy (chemotherapy, radiotherapy, biologic therapy, endocrine therapy, immunotherapy, etc.) within 4 weeks prior to first dose Received small-molecule targeted therapy or oral fluorouracil-based agents within 2 weeks prior to first dose or within 5 half-lives (whichever is longer) Received Chinese herbal medicine or proprietary Chinese medicine with antitumor indications within 2 weeks prior to first dose Received Chinese herbal medicine or proprietary Chinese medicine with antitumor indications within 2 weeks prior to first dose Received nitrosourea or mitomycin C within 6 weeks prior to first dose Palliative radiotherapy for non-target lesions is permitted (≥2 weeks prior to first dose)
• Uncontrolled hypertension, pulmonary hypertension, or unstable angina myocardial infarction, coronary artery bypass grafting, or stenting within 6 months prior to dosing history of chronic heart failure at New York Heart Association (NYHA) functional class III-IV Severe arrhythmias requiring treatment (excluding atrial fibrillation or paroxysmal supraventricular tachycardia deemed by the investigator to have no impact on the trial), including QTcF ≥ 450 ms in males or ≥ 470 ms in females (calculated using Fridericia's formula) cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to enrollment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Cancer Hospital Chinese Academy of Medical Scienc — Langfang

Identifiers

NCT: NCT07656116 · VSV-A01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗