| Eligibility |
Inclusion Criteria:
- 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:
1. 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);
2. Liver function: TBIL=1.5×ULN, ALT=5×ULN, AST=5×ULN;
3. Child-Pugh A or better B (= 7);
4. Renal function: Cr=1.5×ULN, and creatinine clearance = 45ml/min (calculated
according to Cockcroft-Gault formula);
5. 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.
Exclusion Criteria:
- 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.
- Patients with central nervous system metastasis, spinal cord metastasis and/or spinal
cord compression are not suitable for inclusion according to the investigator's
judgment.
- 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:
1. Ventricular arrhythmias requiring clinical intervention;
2. QTc interval>480ms;
3. Acute coronary syndrome, congestive heart failure, stroke or other grade III or
above cardiovascular events within 6 months;
4. New York Heart Association (NYHA) cardiac function class = class II or left
ventricular ejection fraction (LVEF) <40%;
5. Uncontrolled hypertension (systolic blood pressure =140mmHg, or diastolic blood
pressure =90mmHg after treatment).
- Patients with active or past autoimmune diseases that may relapse (such as
interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis,
hyperthyroidism, hypothyroidism (including but not limited to these diseases or
syndromes, etc.); but does not include patients with clinically stable autoimmune
thyroiditis, autoimmune-mediated hypothyroidism treated with a stable dose of thyroid
replacement hormone; Type I diabetes on insulin; patients with vitiligo or childhood
asthma/allergies that have resolved and do not require any intervention in adulthood.
- Have received immunotherapy and experienced immune-related adverse events (irAEs) such
as immune-related pneumonia, myocarditis, etc., which may affect the safety of the
trial medication as judged by the researcher.
- Known alcohol or drug dependence.
- People with mental disorders or poor compliance.
- Pregnant or lactating women.
- Patients with obvious symptoms and unstable pleural effusion, peritoneal effusion or
pericardial effusion (those with stable clinical symptoms after treatment of pleural
effusion, ascites or pericardial effusion can be included).
- The researcher believes that the subject has other serious systemic diseases or other
reasons and is not suitable to participate in this clinical study.
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