| Eligibility |
Inclusion Criteria:
1. Men or women aged =18 years at the time of signing the Informed Consent Form (ICF);
2. Patients with a definitive histopathological or cytological diagnosis of colorectal
cancer with hepatic metastases who have received and failed at least second-line
standard therapy in the past, or who have been assessed by the investigator to be
unsuitable for standard therapy;
3. Patients with at least one measurable lesion (as defined by RECIST v1.1) that has not
been previously treated with radiotherapy (unless definite progression of the lesion
has occurred after radiotherapy);
4. Eastern Cooperative Oncology Group(ECOG) score 0 or 1;
5. Expected survival = 12 weeks;
6. For female subjects with childbearing potential, a negative serum pregnancy test
within 7 days prior to the first dose of study drug; Acceptance of using medically
accepted and effective contraception for at least 6 months after signing the ICF and
until the last dose of study drug;
7. Male subjects with childbearing potential agree to use medically accepted and
effective contraception from the date of signing the ICF to the date of at least 6
months after the last dose; in addition, the male subject must agree that he will not
donate sperm during this period;
8. Understand and voluntarily sign a written ICF and be willing to comply with all trial
requirements.
Exclusion Criteria:
1. Patients allergic to the study drug (including its components) or other similar
products;
2. Patients who have been treated with oncolytic virus therapy, interleukin-12 (IL-12) in
combination with anti PD-1/ PD-L1;
3. Patients who have not recovered from the adverse reactions of previous treatments (the
treatment-related toxicity = grade 2, except for alopecia, fatigue or other tolerable
events judged by the investigator);
4. Patients with brain metastases that have progressed within 3 months prior to study
drug administration (brain metastases that have stabilised within 3 months may be
included);
5. History of other malignancies (except cured basal cell skin cancer, cervical carcinoma
in situ, papillary thyroid cancer, etc.) within 5 years prior to study drug
administration;
6. Patients who received any antineoplastic drug (including but not limited to
chemotherapy, biologics, herbal preparations, etc.) within 4 weeks or 5 half-lives
(whichever is shorter) prior to study drug administration;
7. Severe hepatic dysfunction (Child Pugh class C), or significant jaundice, hepatic
encephalopathy, refractory pleural effusion, or hepatorenal syndrome; Coagulation:
international normalized ratio (INR) or Prothrombin time (PT) > 1.5 x Upper limits of
normal(ULN) ; activated partial thromboplastin time (aPTT)> 1.5 x ULN; Current
comorbidity with active hepatitis: persistent or active hepatitis B (i.e. HBsAg
positive or hepatitis B virus (HBV) DNA = upper limit of detection), hepatitis C (HCV
RNA = upper limit of detection)] or other hepatitis; Haematology: white blood cell
count (WBC) < 3.0 x 10^9/L; platelets < 75 x 10^9/L; haemoglobin < 80g/L; Renal
function: serum creatinine >1.5 ULN or creatinine clearance <60 mL/min
(Cockcroft-Gault formula calculation)
8. Serious or uncontrollable cardiac disease requiring treatment, congestive heart
failure classified as grade 3 or 4 by the New York Heart Association (NYHA), unstable
angina not controlled by medication, history of myocardial infarction within 6 months
prior to enrolment, serious arrhythmia requiring medication (except atrial
fibrillation or paroxysmal supraventricular tachycardia); History of arterial
thromboembolic event, venous thromboembolic event of grade =3 as defined in NCI CTCAE
5.0, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy
within 6 months prior to randomisation; Current major vascular disease such as aortic
aneurysm, aortic coarctation aneurysm, etc. that may be life-threatening or require
surgery within 6 months;
9. Previous immunotherapy (including but not limited to PD-1/PD-L1) with immune-related
pneumonitis or = grade 3 other immune-related adverse reactions; Current active immune
disease requiring systemic treatment with immunosuppressive agents (excluding
autoimmune diseases such as vitiligo that do not require intervention, or
hypothyroidism that only needs hormone replacement therapy), or immune disease
requiring systemic treatment with immunosuppressive agents (e.g., systemic lupus
erythematosus) that is likely to recur; Patients with other diseases currently
requiring systemic immunosuppressive therapy;
10. HIV Positive; Patients who are currently in the midst of an episode of orofacial
herpes; Clinically significant infection or infection treated with intravenous
antibiotics within 4 weeks prior to dosing;
11. Inability to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting,
diarrhoea or other gastrointestinal disorders that would seriously interfere with drug
administration and absorption;
12. Patients who need anti-herpes simplex virus medications (including, but not limited
to, acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet,
cidofovir, etc.) for the duration of the study, with the exception of topical
applications;
13. History of seizures within 12 months prior to study drug administration;
14. Patients with the history of drug use or a history of substance abuse (including
alcohol) within one year prior to signing the ICF;
15. Pregnant or lactating women;
16. Other reasons judged by the investigator.
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