Safety of Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Tumors

NCT05914376 | Active Not Recruiting Phase 1

• 1 other identifier: hV01-ITu-101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to evaluate the safety, tolerance, pharmacokinetics, and biological properties of recombinant human IL-21-expressing oncolytic vaccinia virus injection (hV01) in patients with advanced solid tumors.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• To assess the Dose-limiting toxicities (DLTs) of hV01.

  To identify dose-limiting toxicities (DLTs) of hV01 administered by single or multiple intratumoral injections.

  From first dose till 28 days after last dose.

• To assess the adverse events (AEs) and tolerability of hV01.

  To assess the frequency, severity, and nature of adverse events (AEs) of hV01 administered by single or multiple intratumoral injections at different dose levels. This will be determined by abnormalities or changes in vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, physical examination, 12-lead electrocardiogram, and laboratory test results.

  From informed consent to approximately 3 months after End of Trial (EOT)

Secondary Outcomes (8)

• Pharmacokinetics of hV01.

  From baseline to 28 days after last dose.

• Expression of IL-21.

  From baseline to 28 days after last dose.

• Viral shedding of hV01.

  From baseline to 28 days after last dose.

• Anti-tumor activity of hV01: overall response rate (ORR).

  From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the end of treatment.

• Anti-tumor activity of hV01: disease control rate (DCR).

  From baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after the end of treatment.

Other Outcomes (4)

• To evaluate the immunogenicity of hV01.

  From baseline to 4 weeks after the End of Treatment.

• To assess immune cells in the peripheral blood

  From baseline to 4 weeks after the End of Treatment.

• To assess cytokine levels in the peripheral blood.

  From baseline to 4 weeks after the End of Treatment.

Study Arms (1)

hV01 intratumoral injection

EXPERIMENTAL

Single-dose phase (3+3 design): Participants will receive an intratumoral injection of hV01 at one of the dose levels from 1.0×10\^7 PFU to 8.0×10\^8 PFU on Day 1 of each treatment cycle. The MTD or MAD will be determined based on the safety and tolerability outcomes of this phase. Multiple-dose phase (3+3 design): 1. Two doses per cycle: Participants will receive two intratumoral injections of hV01 at the dose level of sub-MTD or sub-MAD on Day 1 and Day 8 of each treatment cycle. 2. Three doses per cycle: Participants will receive three intratumoral injections of hV01 at the dose level of sub-MTD or sub-MAD on Day 1, Day 8 and Day 15 of each treatment cycle.

Biological: Recombinant human IL-21-expressing oncolytic vaccinia virus injection

Interventions

Recombinant human IL-21-expressing oncolytic vaccinia virus injection BIOLOGICAL

hV01 is a recombinant vaccinia virus with deletions of the viral thymidine kinase (TK) and viral growth factor (VGF) genes and insertion of the human IL-21 gene.

Also known as: hV01

hV01 intratumoral injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signing an informed consent form.
• Men or women aged 18 to 75 years.
• Histologically and/or cytologically confirmed advanced malignant solid tumors refractory or failed to respond to standard therapy (including disease progression and/or intolerable toxicities).
• At least one measurable lesion according to RECIST v1.1 criteria, which can be injected intratumorally either directly or with the assistance of medical imaging equipment such as B-ultrasound or CT. The baseline longest diameter (shortest diameter for lymph node lesions) of the lesion targeted for injection should be more than 1.5 cm, and the lesion also meets the requirements of the relevant dosing volume.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Life expectancy of at least 3 months.
• Required baseline laboratory data include:
• Hematology: absolute neutrophil count (ANC) ≥ 1.5×10\^9/L, platelet (PLT) count ≥ 75×10\^9/L, hemoglobin (Hb) ≥90 g/L (without supportive therapy within 14 days prior to laboratory test);
• Liver function: serum total bilirubin (TBIL) ≤1.5×ULN (or ≤3×ULN for patients with Gilbert's syndrome or liver metastasis); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN (or\<5×ULN for patients with primary liver cancer or liver metastasis);
• Renal function: serum creatinine (Cr) ≤1.5×ULN, and creatinine clearance (Cockcroft-Gault method) ≥45 mL/min. For men: creatinine clearance = \[\[140-age(yr)\]×weight (kg)\]/\[0.818×creatinine (μmol/L)\]; For women: creatinine clearance = \[\[140-age(yr)\]×weight (kg)×0.85\]/\[0.818×creatinine (μmol/L)\];
• Coagulation test: activated partial thromboplastin time (APTT) ≤1.5×ULN; international normalized ratio (INR) ≤1.5×ULN.
• Female patients of childbearing age must have a negative serum pregnancy test. Female patients of childbearing age and male patients whose partners are of childbearing age must agree to use medically approved contraceptive measures (hormonal or barrier methods or abstinence) throughout the treatment period and also within 3 months after the last dose of the investigational drug. Male patients must also avoid sperm donation.

You may not qualify if:

• Receiving any of the following anti-tumor treatments within a specified time period:
• Systemic anti-tumor treatment, including chemotherapy, large-molecule targeted therapy, immunotherapy, and endocrine therapy within 4 weeks before first dose (within 6 weeks of dosing for nitrosourea or mitomycin C);
• Small-molecule targeted therapy within 2 weeks before first dose or within 5 half-lives of the small-molecule targeted drug (whichever is longer);
• Traditional Chinese medicine or Chinese herbal medicine used as anti-tumor agent within 2 weeks before first dose;
• Radiotherapy (excluding palliative radiotherapy) within 2 weeks before first dose;
• Prior oncolytic virus treatment.
• Acute toxic effects from prior treatments not resolved to Common Terminology Criteria for Adverse Events (CTCAE, v5.0) grade 1 or below, except for toxicities deemed safe by the investigator, such as alopecia.
• Patients with clinical symptoms of central nervous system (CNS) metastasis or meningeal metastasis, or other evidence indicating that CNS or meningeal metastases are not controlled.
• Known or suspected active autoimmune diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, and Hashimoto's thyroiditis).
• Previous allogeneic stem cell or organ transplantation.
• History of severe cardiovascular and cerebrovascular diseases, including:
• Acute coronary syndrome (including myocardial infarction, severe or unstable angina), myocarditis, congestive heart failure, cerebrovascular accidents, or other cardiovascular events of CTCAE (v5.0) grade 3 or higher within 12 months of dosing;
• Severe arrhythmia requiring clinical intervention (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes), corrected QT interval (QTc) \>450 ms for males or \>470 ms for females, or a family history of long QT syndrome;
• New York Heart Association (NYHA) classification of class II or above, or left ventricular ejection fraction (LVEF) \<50%;
• Uncontrolled hypertension (as judged by the investigator) or hypotension despite standard treatment.

Sponsors & Collaborators

• Hangzhou Converd Co., Ltd.: lead

Study Sites (2)

Zhejiang People's Hospital

Hangzhou, Zhejiang, China

Location

Fudan University Shanghai Cancer Center

Shanghai, China

Location

Study Officials

• Jian Zhang

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 22, 2023
• Study Start: July 5, 2023
• Primary Completion: July 2, 2025
• Study Completion (Estimated): June 10, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)