Overview

Clinical Study of VG161 in Subjects With Advanced Malignant Solid Tumors

Status:
Recruiting
Trial end date:
2022-12-01
Target enrollment:
0
Participant gender:
All
Summary
VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This Phase I study will be conducted in HSV-seropositive subjects with advanced malignant solid tumors that are refractory to conventional therapies. This is an open label study to determine the safety and tolerability of VG161, and recommended dose of VG161 for Phase II trials.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
CNBG-Virogin Biotech (Shanghai) Ltd.
Criteria
Inclusion Criteria:

1. Males or females aged within 18 to 80 years.

2. Subject with late stage carcinoma which is refractory/relapsed after and/or intolerant
of standard therapies or for which no standard therapy exists.

3. There is at lease one injectable tumor lesion that meet the requirements of the
assigned dose level. The superficial lesions are preferred, and the deep lesions that
can be injected under the guidance of B ultrasound or computed tomography (CT) scan
can also be selected.

4. Eastern Cooperative Oncology Group (ECOG) scores 0 or 1.

5. Life expectancy is at least 3 months.

6. Required organ function:

1) Hematology blood (no blood transfusion or colony stimulating factor treatment within 14
days): Absolute neutrophil count (ANC)≥1.5×10^9L, Platelets ( PLT)≥75×10^9L, hemoglobin
(Hb)≥85g/L; 2) Liver function: Total Serum bilirubin (TBIL)≤1.5×ULN (the upper limit of the
reference range), Alanine aminotransferase (ALT)≤3×ULN, aspartate aminotransferase
(AST)≤3×ULN (acceptable for patients with liver metastasis or liver cancer: TBIL≤5×ULN,
AST≤5×ULN, ALT≤5×ULN); 3) Renal function: Serum creatinine≤1.5×ULN, and creatinine
clearance≥50 ml/min (calculated per Cockcroft-Gault formula); 4) Coagulation function:
activated partial thromboplastin time (APTT)≤1.5×ULN, international standardized ratio
(INR)≤1.5×ULN.

7. Subjects of childbearing potential (male and female) must agree to use a reliable
contraceptive method (hormone or barrier method or abstinence) during the study and for at
least 90 days following the last dose; females of childbearing potential must have a
negative blood or urine pregnancy test within 7 days of study enrollment.

8. Signed written informed consent.

Exclusion Criteria:

1. Subject in prior anti-tumor therapies such as chemotherapy, radiotherapy, biotherapy,
endocrinotherapy, targeted therapy, immunotherapy within 4 weeks of study treatment
initiation.

2. Participation in clinical trials of any other investigational agents within 4 weeks of
study treatment initiation.

3. Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks
of study treatment initiation.

4. Patients who received systemic treatment with either corticosteroids ( >10 mg/ daily
prednisone or equivalent) or other immunosuppressive medications within 14 days of
study treatment initiation.

5. Subjects with any ≥Grade 1 toxicity (as per NCI CTC AE Version 5.0) related to prior
anti-cancer therapy (except for toxicity that the investigator assessed to be no
safety risk, such as alopecia.).

6. Subjects with any uncontrolled active Central Nervous System (CNS) metastasis or
meningeal metastasis with clinical symptoms.

7. Seronegative for Herpes Simplex Virus (HSV) (HSV-1IgG and HSV-1IgM).

8. Subjects with the relapse of HSV infection and relevant clinical manifestations, such
as lip herpes, herpes keratitis, herpes dermatitis, and genital herpes.

9. Subjects with other uncontrolled active infections.

10. Known history of immunodeficiency and test positive of human immunodeficiency virus
(HIV).

11. Active infection of hepatitis B (HBV) (hepatitis b virus titer higher than the
detection limit or those requiring antiviral therapy), or hepatitis C virus (HCV).

12. History of severe cardiovascular disease:

1)Ventricular arrhythmias requiring clinical intervention; 2)QTc interval >480 ms; 3)Acute
coronary syndrome, congestive heart failure, stroke or other cardiovascular events of III
grade or above within 6 months; 4)The cardiac function grade≥II or left ventricular
ejection fraction (LVEF) <50% per the New York Heart Association (NYA); 5)Uncontrolled
hypertension. 13. Subjects with active or past autoimmune diseases that are likely to recur
(e.g. systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.); acceptable for
patients with clinically stable autoimmune thyroiditis.

14. Subjects with any prior ≥Grade 3 immune-related adverse event (irAE) while receiving
any previous immunotherapy agent.

15. known to have alcohol or drug dependence. 16. Persons with mental disorders or poor
compliance. 17. Pregnant or lactating women. 18. Subjects with any significant unrelated
systemic illness that to the investigator's opinion would compromise the subject's
eligibility to participate the study.