Clinical Study of VG161 Combined With Camrelizumab in Patients With Advanced Primary Hepatocellular Carcinoma

NCT06124001 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: VG161-C203
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 injection.This study will be conducted in combination with camrelizumab in patients with advanced advanced primary hepatocellular carcinoma who have received at least one first-line treatment regimen. This is an open-label study divided into two parts. Part 1: This part is an escalating dose trial to explore the safety of the combination and determine the recommended safe dose of the combination. Part 2: This part is an extension trial to investigate the preliminary efficacy of the combination at a safe dose.

Conditions

Primary Hepatocellular Carcinoma

Keywords

Primary Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (4)

• Phase Ib:RP2D/MTD

  RP2D/MTD for VG161 in Combination with Camrelizumab

  through Phase Ib study completion, an average of 8 months

• Phase Ib:Incidence and number of DLT

  Incidence and number of DLT (dose-limiting toxicity)

  through Phase Ib study completion, an average of 8 months

• Phase Ib:AE, SAE occurrence and frequency

  Occurrence and frequency of AE (Adverse Event) and SAE（Serious adverse event)

  through Phase Ib study completion, an average of 8 months

• Phase IIa:ORR

  Objective response rate (ORR)

  Time Frame: through Phase IIa study completion, an average of 1 year

Secondary Outcomes (7)

• Phase Ib and Phase IIa:ORR

  through Phase Ib and Phase IIa study completion, an average of 2 year

• Phase Ib and Phase IIa:DCR

  through Phase Ib and Phase IIa study completion, an average of 2 year

• Phase Ib and Phase IIa:PFS

  through Phase Ib and Phase IIa study completion, an average of 2 year

• Phase Ib and Phase IIa:OS

  through Phase Ib and Phase IIa study completion, an average of 2 year

• Phase Ib and Phase IIa:DOR

  through Phase Ib and Phase IIa study completion, an average of 2 year

Study Arms (1)

Experimental: Single Arm

EXPERIMENTAL

VG161: 1)1.0 × 10 \^ 8 PFU daily for 2 consecutive days on Days 1-2 of each cycle (D1-D2); 2)1.0 × 10 \^ 8PFU daily for 3 consecutive days on Days 1-3 of each cycle (D1-D3); camrelizumab: 3 mg/kg every 3 weeks (D8) Part2: Depends on the recommended dose in Part1

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

Interventions

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

Intratumoral injection only. Dosing days may be Days 1-2 or Days 1-3.

Also known as: VG161

Experimental: Single Arm

camrelizumab for Injection DRUG

Administered once at 3 mg/kg intravenously on Days 8 of each cycle.

Also known as: camrelizumab

Experimental: Single Arm

Eligibility Criteria

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

You may qualify if:

• Subjects must give informed consent to this study before the trial and voluntarily sign a written informed consent form.
• Age 18 to 75 (inclusive), gender is not limited.
• Patients with advanced primary hepatocellular carcinoma confirmed by histopathology or cytology.
• According to the CSCO Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition), patients who have received at least previous first-line treatment regimens that have failed treatment (disease progression or inability to tolerate treatment) must have been treated.
• According to RECIST 1.1, it is determined that at least one CT examination shows that it is measurable and meets the requirements of the volume of injection administration (or the volume of first injection administration in phase IIa) that can be injected under ultrasound guidance (preferably the main tumor burden lesion) under ultrasound guidance, and the longest baseline diameter of the injection lesion (short diameter of lymph node lesions) is \>1.5 cm (of which the portal vein lymph node is short, the diameter needs to be \> 20 mm).
• Those with positive herpes simplex virus antibody test results (HSV-1 IgG or HSV-1 IgM).
• ECOG physical status score 0-1.
• Estimated survival time of more than 3 months.
• Have adequate organ function:
• Routine blood (no blood transfusion or colony-stimulating factor therapy within 14 days): ANC≥ 1.5×109/L, PLT≥75×109/L, Hb≥85g/L, lymphocyte count ≥1.5×109/L (for lymphocyte count 0.8×109/L to 1.5×109/L is determined by the investigator whether to enroll);
• Liver function: TBIL≤1.5×ULN, ALT≤5×ULN, AST≤5×ULN;
• Child-Pugh A or better B (≤ 7);
• Renal function: Cr≤1.5×ULN, and creatinine clearance ≥ 45ml/min (calculated according to Cockcroft-Gault formula);
• Coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5×ULN, international normalized ratio (INR) ≤1.5×ULN.
• Eligible subjects of childbearing potential (male and female) must agree to use a reliable method of contraception (hormonal or barrier or abstinence) during the trial and at least 90 days after the last dose (VG161 or carrelizumab, whichever occurs later); Female patients of childbearing age must have a negative blood pregnancy test within 7 days prior to enrollment.

You may not qualify if:

• Known fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma or mixed hepatocellular carcinoma.
• Have received chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy and other anti-tumor drugs within 4 weeks before the first use of study drugs, among which oral fluorouracils and small molecule targeted drugs are the first use of study drugs. Within the first 2 weeks or the 5 half-lives of the drug (whichever is longer).
• Have received other unmarketed clinical trial treatments within 4 weeks before using the study drug for the first time.
• Have undergone major organ surgery (excluding puncture biopsy) or experienced significant trauma within 4 weeks before taking the study drug for the first time.
• Patients who have received systemic corticosteroids (prednisone \>10 mg/day or equivalent doses of similar drugs) or other immunosuppressants within 14 days before the first use of study drugs;Exceptions are the following: treatment with topical, ocular, intraarticular, intranasal, and inhaled corticosteroids; short-term use of corticosteroids (≤10 mg prednisone equivalent) for prophylactic treatment (e.g., prevention of contrast media allergy).
• Have received vaccination within 4 weeks before the first use of study drugs.
• Known severe allergic reaction to any monoclonal antibody.
• The adverse reactions of previous anti-tumor treatments have not returned to CTCAE 5.0 grade ≤1 (except for toxicities such as hair loss that the researcher has judged to have no safety risks).
• Liver tumor burden is greater than 50% of the total liver volume, or those who have received liver transplantation in the past.
• In the period of recurrent infection of herpes simplex virus, with corresponding clinical manifestations, such as cold sores, herpetic keratitis, herpetic dermatitis, genital herpes, etc.
• Other uncontrolled active infections.
• Have a history of immunodeficiency, including positive HIV antibody test and positive Treponema pallidum antibody test.
• Patients with active chronic hepatitis B or active hepatitis C (except hepatitis B virus carriers, stable hepatitis B after drug treatment \[negative HBV-DNA test or \<50IU/ml\] and cured hepatitis C patients \[HCV RNA Tested negative\]).
• Have a history of serious cardiovascular and cerebrovascular diseases:
• Ventricular arrhythmias requiring clinical intervention;

Sponsors & Collaborators

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

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

camrelizumab; Injections

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Tingbo Tingbo, MD. PhD.

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tingbo Liang, MD.PhD.

CONTACT

0571-87236666; liangtingbo@zju.edu.cn

Yinan Shen, MD. PhD.

CONTACT

0571-87236666; fysyn@163.com

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: October 16, 2023
• First Posted: November 9, 2023
• Study Start: November 30, 2023
• Primary Completion: December 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: November 15, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share