Clinical Study of VG161 in Subjects With Advanced Malignant Solid Tumors

NCT04758897 | Unknown Phase 1 DMC

• 1 other identifier: VG161-C101
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Advanced Malignant Solid Tumor

Keywords

Solid Tumor

Outcome Measures

Primary Outcomes (5)

• MTD/RP2D

  MTD (Maximum tolerable dose) / RP2D (Recommended dose for phase II)

  1 month

• Occurence of DLT

  Occurence of DLT (Dose Limiting Toxicity)

  1 month

• Numbers of DLT

  Numbers of DLT (Dose Limiting Toxicity)

  1 month

• Occurence of AE and SAE（NCI CTCAE 5.0）

  Occurence of Adverse Event (AE) and Serious Adverse Event (SAE) （NCI CTCAE 5.0）

  7 months

• Frequency of AE and SAE（NCI CTCAE 5.0）

  Frequency of Adverse Event (AE) and Serious Adverse Event (SAE) （NCI CTCAE 5.0）

  7 months

Secondary Outcomes (9)

• Tmax(h)

  At the end of Cycle 1 (each cycle is 28 days)

• Cmax(copies/ugDNA)

  At the end of Cycle 1 (each cycle is 28 days)

• ORR

  7 months

• DCR

  7 months

• mPFS

  7 months

Study Arms (1)

Single Arm

EXPERIMENTAL

1. 5.0\*10\^7 on D1 2. 1.0\*10\^8 on D1 3. 2.0\*10\^8 on D1 4. 2.0\*10\^8 on D1 and D2 5. 2.0\*10\^8 on Days 1 to 3 6. 2.0\*10\^8 on Days 1 to 4 7. 2.0\*10\^8 on Days 1 to 5

Drug: Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell))

Interventions

Recombinant Human IL12/15-PDL1B Oncolytic HSV-1 Injection (Vero Cell)) DRUG

Intratumoral injection only. The dosing date can be the Day 1 only or Days 1 through 5.

Also known as: VG161

Single Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged within 18 to 80 years.
• Subject with late stage carcinoma which is refractory/relapsed after and/or intolerant of standard therapies or for which no standard therapy exists.
• 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.
• Eastern Cooperative Oncology Group (ECOG) scores 0 or 1.
• Life expectancy is at least 3 months.
• Required organ function:
• \) 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.
• \. 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.
• \. Signed written informed consent.

You may not qualify if:

• Subject in prior anti-tumor therapies such as chemotherapy, radiotherapy, biotherapy, endocrinotherapy, targeted therapy, immunotherapy within 4 weeks of study treatment initiation.
• Participation in clinical trials of any other investigational agents within 4 weeks of study treatment initiation.
• Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks of study treatment initiation.
• 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.
• 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.).
• Subjects with any uncontrolled active Central Nervous System (CNS) metastasis or meningeal metastasis with clinical symptoms.
• Seronegative for Herpes Simplex Virus (HSV) (HSV-1IgG and HSV-1IgM).
• Subjects with the relapse of HSV infection and relevant clinical manifestations, such as lip herpes, herpes keratitis, herpes dermatitis, and genital herpes.
• Subjects with other uncontrolled active infections.
• Known history of immunodeficiency and test positive of human immunodeficiency virus (HIV).
• 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).
• History of severe cardiovascular disease:
• )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.
• \. Subjects with any prior ≥Grade 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent.
• \. 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.

Sponsors & Collaborators

• CNBG-Virogin Biotech (Shanghai) Ltd.: lead

Study Sites (2)

ShangHai East hospital

Shanghai, Shanghai Municipality, China

RECRUITING

Xin Hua Hospital Affiliated to ShangHai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

RECRUITING

Study Officials

• Jin Li, doctor

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Li, doctor

CONTACT

13761222111; lijin@csco.org.cn

Study Design

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

Study Record Dates

• First Submitted: February 9, 2021
• First Posted: February 17, 2021
• Study Start: April 14, 2021
• Primary Completion: March 14, 2022
• Study Completion: December 1, 2022
• Last Updated: April 27, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)