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.
Part1(Phase Ib primary objective): To evaluate the safety and tolerability of VG161 administered by intratumoral injection combined with camrelizumab in the treatment of patients with advanced advanced primary hepatocellular carcinoma who have received at least one first-line treatment regimen. explore the most suitable recommended Phase II dose (RP2D) for combination therapy, and determine the recommended regimen for combination therapy in Phase IIa clinical trials. Secondary objectives:1) Preliminary evaluation of the anti-tumor activity of VG161 combined with camrelizumab in the treatment of patients with advanced primary hepatocellular carcinoma;2) Monitor changes in immunological indicators related to pharmacodynamics;3) Evaluate the impact of herpes simplex virus type I antibody titer levels on the safety and effectiveness of VG161. Part2(Phase IIa Primary Objective): To evaluate the efficacy of VG161 in combination with carrelizumab in the treatment of patients with advanced primary hepatocellular carcinoma, the main observation index was objective response rate (ORR). Secondary objectives: 1) secondary observations to evaluate the efficacy of combination therapy, including disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and duration of remission (DOR);2) monitoring changes in pharmacodynamic-related immunological indicators;3) To further evaluate the safety of VG161 in combination with carrelizumab.4) To evaluate the effect of herpes simplex virus type I antibody titer level on the safety and efficacy of VG161
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Intratumoral injection only. Dosing days may be Days 1-2 or Days 1-3.
Administered once at 3 mg/kg intravenously on Days 8 of each cycle.
Phase Ib:RP2D/MTD
RP2D/MTD for VG161 in Combination with Camrelizumab
Time frame: 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)
Time frame: 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)
Time frame: through Phase Ib study completion, an average of 8 months
Phase IIa:ORR
Objective response rate (ORR)
Time frame: Time Frame: through Phase IIa study completion, an average of 1 year
Phase Ib and Phase IIa:ORR
Objective response rate (ORR)
Time frame: through Phase Ib and Phase IIa study completion, an average of 2 year
Phase Ib and Phase IIa:DCR
disease control rate (DCR)
Time frame: through Phase Ib and Phase IIa study completion, an average of 2 year
Phase Ib and Phase IIa:PFS
Progression Free Survival (PFS)
Time frame: through Phase Ib and Phase IIa study completion, an average of 2 year
Phase Ib and Phase IIa:OS
Overall Survival (OS)
Time frame: through Phase Ib and Phase IIa study completion, an average of 2 year
Phase Ib and Phase IIa:DOR
Duration of Response (DOR)
Time frame: through Phase Ib and Phase IIa study completion, an average of 2 year
Phase Ib and Phase IIa: Immunological indicators
Immunological parameters: peripheral blood lymphocyte subsets (CD3 +, CD4 +, CD8 +, CD4 +/CD8 + ratio, CD19 +,CD16 + CD56 + (NK) cells), cytokines (IL-12, IL-15, IL-6, TNF-α, IFN-γ)
Time frame: through Phase Ib and Phase IIa study completion, an average of 2 year
Phase Ib and Phase IIa: herpes simplex virus type I antibodies
Titers of herpes simplex virus type I antibodies
Time frame: through Phase Ib and Phase IIa study completion, an average of 2 year
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