| Eligibility |
Inclusion Criteria:
1. Age 18 to 75 years old (including boundary values), male or female;
2. Patients with advanced colorectal adenocarcinoma (Stage IV) with a definite
histological or cytological diagnosis;
3. Partial response (PR) or stable disease (SD) was evaluated in advanced colorectal
cancer patients after 16 to 24 weeks of first-line treatment with fluorouracil-based
chemotherapy combined with or without targeted drugs, and before the last chemotherapy
to trial drug administration;
4. The physical status score of the Eastern Oncology Consortium (ECOG) was 0~1;
5. Have at least one measurable or evaluable lesion according to RECIST 1.1;
6. There are lesions suitable for intratumoral injection;
7. At least 2 weeks and no more than 4 weeks after the end of the last first-line
chemotherapy;
8. Expected survival =12 weeks;
9. Patients with asymptomatic BMS after treatment who are free of disease progression by
computed tomography (CT) or magnetic resonance imaging (MRI), stable for at least 12
weeks and without steroid medication for at least 4 weeks;
10. Laboratory examination (no blood transfusion or use of blood products, no correction
therapy with granulocyte colony stimulating factor or other hematopoietic stimulating
factor within 14 days prior to the first dose) :
1. WBC=3.0×109/L, ANC=1.5×109/L, PLT=100×109/L, Hb=90 g/L;
2. Serum creatinine =1.5×ULN;
3. TBIL=1.5×ULN;
4. ALT and AST=2.5×ULN; Patients with liver metastasis =5×ULN;
5. Normal coagulation: International normalized ratio INR=1.5×ULN or prothrombin
time (PT, APTT) =1.5×ULN;
11. For patients with herpes, it takes 3 months after the herpes subsides;
12. I have fully understood the research and voluntarily signed the informed consent, and
I expect good compliance;
13. For women of childbearing age, the blood pregnancy test must be negative within 7 days
before the first medication;
14. The use of at least one medically approved contraceptive method (e.g. surgical
sterilization, oral contraceptives, intrauterine devices, controlled sexual desire or
barrier contraception combined with spermicide) by fertile women and men with a
partner of a woman of reproductive age for at least six months from the signing of the
informed consent form until the last trial drug treatment.
Exclusion Criteria:
1. Patients who plan to undergo radical excision of metastatic lesions;
2. Unrelieved intestinal obstruction or malabsorption syndrome;
3. Adverse reactions caused by first-line chemotherapy drugs did not recover to = grade 1
before randomization (except hair loss and peripheral neurotoxicity less than or equal
to grade 2);
4. Cardiovascular disease meets one of the following criteria: Congestive heart failure
with =NYHA Level III heart function; Severe arrhythmias requiring medical treatment;
Acute myocardial infarction, severe or unstable angina, coronary or peripheral artery
bypass grafting, or stenting within 6 months prior to initial administration; Left
ventricular ejection fraction (LVEF) <50%; Adjusted QTc interval (Fridericia formula
correction) >450 ms for men and >470 ms for women, or risk factors for tip twisting
ventricular tachycardia such as clinically significant hypokalemia as determined by
the investigator, a family history of long QT syndrome, or a family history of
arrhythmia (such as pre-excited syndrome); High blood pressure that is not effectively
controlled;
5. Patients had active infection or unexplained fever >38.5? during screening or before
initial administration;
6. Patients with congenital or acquired immune deficiency (such as HIV infection),
syphilis antibody positive and syphilis rapid plasma reactin-positive, active
hepatitis (hepatitis B: HBsAg positive and HBV DNA=2000 IU/mL; Hepatitis C: HCV
antibody positive and HCV virus copy number > upper limit of normal);
7. Had received or was receiving or still required to receive other experimental agents
or antiviral therapy within 4 weeks before randomization (hepatitis B patients were
treated with entecavir, tenofovir fumarate dipifurofurl, adefovir dipivoxil
sustainably);
8. Participated in other clinical studies within 4 weeks prior to randomization;
9. Known to be allergic to the test drug or its active ingredients or excipients, or
severely allergic;
10. A known history of psychotropic substance abuse, alcohol or drug abuse;
11. Patients who developed other malignant tumors within 5 years prior to inclusion,
except for cervical carcinoma in situ, low-risk gastrointestinal stromal tumor, in
situ or early stage breast cancer, basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, and papillary carcinoma of the thyroid, which were effectively
resected and required no further antitumor therapy and had a recurrence survival rate
of more than 70% in 5 years;
12. Patients with active autoimmune disease or a history of autoimmune disease that may
recur, but patients with the following diseases are not excluded and can be further
screened:
1. Type 1 diabetes
2. Hypothyroidism (if controlled with hormone replacement therapy alone)
3. Controlled celiac disease
4. Skin diseases that do not require systemic treatment (e.g. vitiligo, psoriasis,
hair loss)
13. Patients for any condition requiring systemic therapy with glucocorticoids (prednisone
>10 mg/ day or equivalent dose of the same drug) or other immunosuppressant within 14
days prior to the administration of the investigational drug, but who are currently or
previously on any of the following steroid regimens may be enrolled:
1. Epinephrine substitute steroid (prednisone =10 mg/ day or equivalent dose of
similar drugs)
2. Systemic absorption of minimal amounts of local, ocular, intra-articular,
intranasal or inhaled corticosteroids
3. Prophylactic short-term (=7 days) use of corticosteroids (e.g., allergy to
contrast media) or to treat non-autoimmune conditions (e.g., delayed
hypersensitivity caused by contact allergens)
14. Patients with grade 2 or above radiation pneumonia during previous antitumor therapy,
or pulmonary diseases such as pulmonary fibrosis history, interstitial pneumonia,
pneumoconiosis, drug-related pneumonia, and severe impairment of lung function;
15. Pleural effusion or ascites with clinical symptoms requiring repeated drainage (=1
time/month);
16. Other researchers did not consider it appropriate to participate in this study.
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