Oncolytic vaccinia virus (hV01) plus PD-1 drug tislelizumab for advanced solid tumors

A Study Evaluating the Safety and Efficacy of hV01, a Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus, in Combination With the PD-1 Inhibitor Tislelizumab for Advanced Solid Tumors.

This trial will test whether adding an IL-21–expressing oncolytic vaccinia virus (hV01) to the PD‑1 drug tislelizumab is safe and can shrink tumors in adults with advanced solid cancers that no longer respond to standard treatments.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Hangzhou Converd Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, Tislelizumab
• Locations: 1 site (Xiamen, Fujian)
• Trial ID: NCT07185243 on ClinicalTrials.gov

What this trial studies

This is a single-arm, two-part trial using intratumoral injections of a recombinant IL-21–expressing oncolytic vaccinia virus (hV01) alone in Part A to define tolerability and dosing frequency and then combined with the PD‑1 inhibitor tislelizumab in Part B. Part A compares two dosing schedules (twice versus three times per 28‑day cycle) using a 3+3 design to monitor dose‑limiting toxicities. Part B administers hV01 multiple times in 42‑day cycles with tislelizumab given on days 14 and 35 and also includes early DLT monitoring for initial subjects. Tumor responses are measured using RECIST v1.1 criteria and safety labs and performance status are closely followed.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 years old with histologically confirmed advanced solid tumors refractory to standard therapy, ECOG 0–1, at least one measurable lesion suitable for intratumoral injection, and adequate organ function.

Not a fit: Patients who lack injectable lesions, have poor performance status (ECOG >1), inadequate blood or liver function, or contraindications to immunotherapy or intratumoral procedures are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could provide a new treatment option that boosts anti‑tumor immune activity and produces tumor shrinkage for patients with refractory advanced solid tumors.

How similar studies have performed: Other early‑phase studies combining oncolytic viruses with PD‑1 inhibitors have shown promising responses in some tumor types, but results have varied and larger trials are still needed.

Eligibility criteria

Inclusion Criteria:

1. Signing an informed consent form.
2. Men or women aged 18 to 75 years.
3. Histologically and/or cytologically confirmed advanced solid tumors refractory or failed to respond to standard therapies.
4. At least one measurable lesion according to RECIST v1.1 criteria, which is suitable for intratumoral injection of hV01 either directly or with the assistance of B-ultrasound, or CT scan. The baseline longest diameter of the lesion targeted for injection should be more than 1.5 cm.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
6. Life expectancy of at least 6 months.
7. Required baseline laboratory data include: (1) Hematology: absolute neutrophil count (ANC) ≥ 1.5×10\^9/L, platelet (PLT) count ≥ 75×10\^9/L, hemoglobin (Hb) ≥90 g/L; (2) 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); (3) 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\]/\[0.818×creatinine (μmol/L)\]; (4) Coagulation test: activated partial thromboplastin time (APTT) ≤1.5×ULN; international normalized ratio (INR)≤1.5×ULN.
8. Female patients of childbearing age must have a negative serum pregnancy test. Note: non-childbearing potential as defined by at least one of the following criteria: surgeries resulted in permanent sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or are post-menopausal; For females aged 50 or older, they will be considered menopausal if they are in amenorrhea, defined as the absence of menstruation for the previous 12 months before screening, which is not caused by any disease; For females younger than 50 years, they will be considered menopausal if they satisfy all the following requirements during screening: they are in amenorrhea, defined as the absence of menstruation for the previous 12 months after termination of hormone treatment, and they have a serum FSH level within the laboratory's reference range for postmenopausal females.

Exclusion Criteria:

1. Receiving any of the following anti-tumor treatments within a specified time period: (1) Systemic anti-tumor treatment, including chemotherapy, large-molecule targeted therapy, immunotherapy, and endocrine therapy within 4 weeks before first dose of hV01 (within 6 weeks of dosing for nitrosourea or mitomycin C); (2) Small-molecule targeted therapy within 2 weeks before first dose of hV01 or within five half-lives of the small-molecule targeted drug (whichever is longer); (3)Radiotherapy (excluding palliative radiotherapy) within 2 weeks before first dose of hV01. (4) previous treatment with an oncolytic virus.
2. Receiving any investigational drugs for clinical trials within 4 weeks prior to the first dose of hV01.
3. 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.
4. 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).
5. Patients who have received an allogeneic stem cell transplant or organ transplant.
6. Patients with a history of severe cardiovascular and cerebrovascular diseases, including: (1) 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 first hV01 dosing; (2) Severe arrhythmia requiring clinical intervention; (3) New York Heart Association (NYHA) classification of class II or above, or left ventricular ejection fraction (LVEF) \<50%; (4) Uncontrolled hypertension or hypotension despite standard treatment.
7. Clinically significant and/or rapidly accumulating pericardial and/or pleural effusion.
8. Bleeding symptoms of great clinical significance or clear bleeding tendency within six months prior to the initial dose of hV01.
9. Severe inflammatory skin diseases that require treatment with medicines (e.g., eczema or psoriasis requiring systematic treatment).
10. 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.
11. 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).
12. Receiving therapeutic dosages of corticosteroids such as prednisone or its equivalent \>10 mg daily within two weeks prior to the first dose of hV01, or having any coexisting diseases that might require systemic corticosteroids or any other immune suppressors during the study (assessed by the investigators) with the following exceptions: local administration of glucocorticoid (e.g. topical routes such as for eyes, intra-articular, intranasal, or inhaled); or usage of glucocorticoids for a short period of time for preventive purposes such as for the prevention of contrast media hypersensitivity).
13. Receiving any of the live vaccines within four weeks of the first dose of hV01.
14. Patients with a history of severe allergies.
15. Mental disorders that could potentially impact the participant's ability to comply with the study requirements.

Where this trial is running

Xiamen, Fujian

• Xiamen Humanity Hospital — Xiamen, Fujian, China (Recruiting)

Study contacts

• Principal investigator: Cheng Huang — Xiamen Humanity Hospital
• Study coordinator: Jun Qiu

Conditions Advanced Solid Tumors