| Eligibility |
Inclusion Criteria:
- Age =18 years old, both sexes;
- Patients with histologically or cytologically confirmed unresectable and metastatic
CRC
- Non-isolated hepatic metastasis: including no liver metastasis or liver metastasis
accompanied by other metastatic lesions, such as lung metastasis, peritoneal
metastasis, etc
- Before enrollment, the tumor tissue was pMMR by immunohistochemistry, or MSS or MSI-L
by PCR or NGS;
- Have received standard treatment in the past and developed disease progression or
intolerance to standard treatment based on RECIST 1.1 during or after standard
treatment. Standard treatment should include:
1. Fluorouracil, oxaliplatin and irinotecan
2. With or without anti-VEGF monoclonal antibody
3. For RAS wild-type patients, combined with anti-EGFR monoclonal antibody
4. For patients with BRAF mutations, BRAF inhibitor therapy is recommended when
drugs are available
- Patients with ECOG score of 0-2 and expected survival time =3 months, patients who can
cooperate to observe adverse reactions and efficacy;
- At least one measurable tumor lesion according to RECIST 1.1 criteria
- Good organ function:
1. neutrophil =1.5*109/L; Platelet =100*109/L; Hemoglobin =9g/dl; Serum albumin
=3g/dl;
2. Thyroid stimulating hormone (TSH) = 1 times the upper limit of normal, T3 and T4
in the normal range;
3. bilirubin = 1.5 times the upper limit of normal value; ALT and AST= 2 times the
upper limit of normal;
4. Serum creatinine = 1.5 times the upper limit of normal, creatinine clearance
=60ml/min;
5. International normalized ratio (INR) or prothrombin time (PT) = 1.5 times the
upper limit of the normal range, unless the patient is receiving anticoagulant
therapy and the PT value is within the intended range for anticoagulant therapy;
6. Activated partial thromboplastin time (aPTT) = 1.5 times the upper limit of
normal;
- There were no serious concomitant diseases that could make the survival time less than
5 years;
- Negative pregnancy test in female subjects (for female patients of childbearing
potential); Infertile female patients;
- Male patients of childbearing potential and female patients of childbearing potential
and at risk of pregnancy must agree to use adequate contraception for the entire
duration of the study and for 12 months after receiving treatment with the protocol;
- Signed and dated informed consent indicating that the patient has been informed about
all relevant aspects of the study;
- Patients who are willing and able to comply with the visit schedule, treatment plan,
laboratory tests, and other study procedures;
- Willing to comply with the arrangement during the study period can not participate in
any other clinical research on drugs and medical devices
Exclusion Criteria:
- Pathological diagnosis of other intestinal tumors, such as gastrointestinal stromal
tumor;
- Tumor tissues were dMMR detected by immunohistochemistry, or MSI-H detected by PCR or
NGS
- Prior treatment with PD-1 antibody, PD-L1 antibody, or CTLA-4 antibody;
- Previous or concurrent history of other malignant tumors, excluding adequately treated
non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma;
- Active autoimmune disease, history of autoimmune disease (such as interstitial
pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism,
hypothyroidism, including but not limited to these diseases or syndromes); It does not
include autoimmune-mediated hypothyroidism treated with stable doses of thyroid
replacement hormone; Type I diabetes on stable doses of insulin; Vitiligo or cured
childhood asthma/allergy without any intervention in adulthood;
- A history of immunodeficiency, including HIV positive, other acquired or congenital
immunodeficiency diseases, or organ transplantation or allogeneic bone marrow
transplantation;
- Contraindications to antiangiogenic drugs (such as active bleeding, gastrointestinal
bleeding, hemoptysis, etc.);
- History of interstitial lung disease (excluding radiation pneumonitis without steroid
treatment) and non-infectious pneumonia;
- Patients with active pulmonary tuberculosis infection detected by medical history or
CT examination, or with a history of active pulmonary tuberculosis infection within 1
year before enrollment, or with a history of active pulmonary tuberculosis infection
more than 1 year before enrollment but without regular treatment;
- The subject has active hepatitis B (HBV DNA =2000 IU/mL or 104 copies/mL), hepatitis C
(hepatitis C antibody positive and HCV-RNA above the detection limit of the assay)
- Severe cardiopulmonary and renal dysfunction;
- Have hypertension that is not well controlled with antihypertensive medication
(systolic blood pressure =140mmHg or diastolic blood pressure =90mmHg);
- A history of psychotropic substance abuse, alcohol or drug abuse;
- Other factors that may affect subject safety or trial compliance as judged by the
investigator. Severe medical conditions requiring concomitant treatment (including
mental illness), serious laboratory abnormalities, or other family or social factors
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