Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Pancreatic Cancer

Official title

A Phase II Trial to Evaluate the Efficacy of Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Patients With Advanced Pancreatic Tumors

Overview

The main goal of this clinical trial is to preliminary evaluate the efficacy of recombinant human IL-21-expressing oncolytic vaccinia virus injection (hV01) in patients with advanced pancreatic cancer.And the secondary purpose is to evaluate the safety of hV01.

Detailed description

This is a single-site, single-arm, open-label,exploratory phase Ⅱa study. Based on the safety results of the completed phase I clinical trial of hV01 , 8.0x10 \^ 8 PFU was selected as a dose level of the dosage for each administration in this clinical trial, hV01 will be administered with twice per cycle (on day 1 and day 15), efficacy evaluation will be conducted on day 28, and every 28 days as a treatment cycle,during which safety will be observed.

Interventions

• Biological Recombinant human IL-21-expressing oncolytic vaccinia virus injection
  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.

Primary outcome measures

• Anti-tumor activity of hV01: overall response rate (ORR). [Time frame: 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). [Time frame: 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: duration of response (DOR). [Time frame: 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.]

Secondary outcome measures (3)

• Anti-tumor activity of hV01: progression-free survival (PFS). [Time frame: 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.]
• Preliminary efficacy of hV01: overall survival (OS). [Time frame: From signing informed consent form until the date of death from any cause, assessed up to 2 years after the end of treatment.]
• To assess the adverse events (AEs) and tolerability of hV01. [Time frame: From informed consent till 28 days after first dose.]

Eligibility criteria

Inclusion criteria

• Signing an informed consent form.
• Men or women aged 18 to 75 years.
• Histologically and/or cytologically confirmed advanced malignant advanced pancreatic 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 Endoscopic ultrasound. 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.
• Required baseline laboratory data include:

a) 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); b) Liver function: serum total bilirubin (TBIL) ≤1.5×ULN (or ≤3×ULN for patients with liver metastasis); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN (or<5×ULN for patients with primary liver cancer or liver metastasis); c) 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\]/\[0.818×creatinine (μmol/L)\]; d) 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.

Exclusion criteria

• Receiving any of the following anti-tumor treatments within a specified time period:

a) 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); b) Small-molecule targeted therapy within 2 weeks before first dose or within 5 half-lives of the small-molecule targeted drug (whichever is longer); c) Traditional Chinese medicine or Chinese herbal medicine used as anti-tumor agent within 2 weeks before first dose; d) Radiotherapy (excluding palliative radiotherapy) within 2 weeks before first dose; e) 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).
• History of severe cardiovascular and cerebrovascular diseases, including:

a) 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; b) 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; c) New York Heart Association (NYHA) classification of class II or above, or left ventricular ejection fraction (LVEF) <50%; d) Uncontrolled hypertension (as judged by the investigator) or hypotension despite standard treatment.

• Any uncontrolled active infection requiring systemic anti-infective therapy (graded 2 or higher according to CTCAE v5.0), including but not limited to active tuberculosis, sepsis, bacteremia, fungemia, and viremia.
• Any of the following infections: human immunodeficiency virus (HIV), syphilis spirochete(TP), active hepatitis C (positive HCV RNA test) or active hepatitis B (positive HBsAg and HBV DNA ≥ 2000 IU/mL or ≥10\^4 copies/mL).
• Use of immunomodulatory drugs within 2 weeks of dosing, including but not limited to thymosin, interleukin, interferon.
• Pregnant or lactating women.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Affiliated Hangzhou First People's Hospital,School of Medicine,Westlake University — Hangzhou

Identifiers

NCT: NCT07006077 · hV01-ITu-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗