| Eligibility |
Inclusion Criteria:
-1. age: 18-70 years, of either sex 2. pathologically confirmed locally advanced or
metastatic gastrointestinal tumour (stage III or IV according to AJCC 8th edition staging)
with at least one measurable lesion (meeting RECIST 1.1 criteria) 3. ECOG PS: 0-1 points 4.
have adequate organ and bone marrow function, i.e. meet the following criteria.
1. Routine blood test criteria to be met.
1. HB = 90g/L.
2. ANC =1.5×109/L.
3. PLT =90 x 109/L.
4. Absolute value of lymphocytes + monocytes >2.0*10^9/L.
2. Biochemical tests are required to meet the following criteria.
1. Total bilirubin = 1.5 times the upper limit of normal (ULN).
2. ALT and AST = 2.5ULN.
3. serum Cr = 1 ULN and endogenous creatinine clearance > 60 ml/min (Cockcroft-Gault
formula).
5. international normalised ratio (INR) = 1.5 and partial thromboplastin time
(PPT or APTT) = 1.5 ULN within 7 days prior to enrolment 6. expected survival of
= 3 months. 7. signed informed consent form (ICF) prior to study enrolment. 8
Women of childbearing potential must have had a pregnancy test (serum or urine)
within 7 days prior to enrolment and have a negative result. Female patients of
childbearing age or male patients whose sexual partners are women of childbearing
age are required to use effective contraception throughout the treatment period
and for 6 months after the last dose.
Exclusion Criteria:
- 1. known hypersensitivity to any of the components of the anti-PD-1 antibody
formulation; or previous severe allergic reactions to other monoclonal
antibodies.
2. diagnosis of other malignancies, excluding radically treated basal cell
carcinoma of the skin, squamous cell carcinoma of the skin and/or radically
resected carcinoma in situ, within 5 years prior to the first dose 3.
Subjects who have been treated with an antitumour vaccine or other
antitumour agents with immunostimulatory effects (interferon, interleukin,
thymidine, immune cell therapy, etc.) within 1 month prior to the first
dose.
4. CNS metastases with symptoms. Subjects may be enrolled in the study if
their CNS metastases have been treated, e.g., clinical stability (MRI
detection) has been maintained for at least 4 weeks, and the subject's
clinical symptoms, such as neurological symptoms, are able to return to
baseline levels at least 2 weeks prior to the first dose (except for
residual signs or symptoms related to CNS treatment). In addition, subjects
receiving stable or tapered doses of =10 mg/day of prednisone (or
equivalent) for at least 2 weeks for clinical symptoms associated with
treatment with corticosteroids are not eligible for enrollment in the study,
otherwise they cannot be enrolled.
5. Acute or chronic active hepatitis B (defined as positive HBsAg for
hepatitis B virus surface antigen at screening) or hepatitis C infection.
Patients with previous hepatitis B virus (HBV) infection or cured HBV
infection (defined as hepatitis B core (HBc) antibody positive and HBsAg
negative) who are negative for HBV DNA only may be enrolled in this study.
HBV DNA testing must be performed on this group of patients prior to
enrolment. Patients who are positive for hepatitis C virus (HCV) antibodies
and negative for HCV RNA only by polymerase chain reaction may be enrolled
in the study. Patients who are antigen-positive but have DNA/RNA copy
numbers within the permissible range should be considered for antiviral
treatment if enrolled in this study and DNA/RNA levels should be monitored
in real time for the duration of the study.
6. previous and current history of pulmonary fibrosis, interstitial
pneumonia, pneumoconiosis, drug-related pneumonia, severely impaired lung
function and other lung diseases.
7. active tuberculosis (TB), on anti-TB treatment or who have received
anti-TB treatment within 1 year prior to the first dose 8. Human
immunodeficiency virus (HIV) infected (HIV-positive), known syphilis
infection 9. Patients who are considered to be at high medical risk due to
severe, uncontrollable disease, non-metastatic systemic disease or having an
active, uncontrollable infection. Some examples include, but not all,
uncontrolled ventricular arrhythmias, recent (within 3 months) myocardial
infarction, uncontrollable grand mal seizures, unstable spinal cord
compression, superior vena cava syndrome, HRCT suggestive of extensive
bilateral interstitial lung disease or any mental illness that may prevent
informed consent from being obtained 10. active autoimmune disease requiring
systemic therapy (e.g. use of disease-relieving drugs, corticosteroids or
immunosuppressants) that occurred within 2 years prior to the first dose
Alternative therapies (e.g. thyroxine, insulin or physiological
corticosteroids for adrenal or pituitary insufficiency, etc.) are permitted
Known history of primary immunodeficiency. Patients with positive autoimmune
antibodies only need to confirm the presence of autoimmune disease at the
discretion of the investigator.
11. Use of immunosuppressive drugs within 4 weeks prior to first dose,
excluding topical glucocorticoids by nasal spray, inhalation or other routes
or physiological doses of systemic glucocorticoids (i.e. not more than 10
mg/day prednisone or equivalent doses of other glucocorticoids), temporary
use of glucocorticoids for the treatment of symptoms of dyspnea in
conditions such as asthma, chronic obstructive pulmonary disease is
permitted.
12. exclude subjects who have undergone major surgical procedures within 4
weeks prior to first dose, non-thoracic radiation therapy >30 Gy within 4
weeks prior to first dose, chest radiation >30 Gy within 24 weeks prior to
first dose, and palliative radiation <30 Gy within 2 weeks prior to first
dose who have not recovered from the toxicity and/or complications of these
interventions to NCI-CTC AE =1 degree (except alopecia and fatigue excluded)
in subjects. Palliative radiotherapy for symptom control is permitted and
must be completed at least 2 weeks prior to the start of treatment with the
study drug and no additional radiotherapy is planned for the same lesion.
For patients who have received radiotherapy prior to 2 weeks prior to the
first dose, all of the following conditions must be met for enrolment:
absence of any current radiotherapy-related toxic effects, no need for
glucocorticoids, exclusion of radiation pneumonia, radiation hepatitis,
radiation enteritis, etc.
13. Pregnant or breastfeeding women. 14. Participated in a clinical trial of
another drug within four weeks. 15. Not considered suitable for inclusion by
the investigator. Exclude subjects with a history or current evidence of any
disease, treatment or laboratory abnormality that may confound the results
of the study, interfere with the subject's participation in the study
procedures or is not in the best interest of the subject's participation in
the study.
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