| Eligibility |
Inclusion Criteria:
1. Males or females aged = 18 to = 75 years at the time of signing informed consent.
2. Imaging examination confirmed unresectable locally advanced or metastatic gastric
cancer (GC) or gastroesophageal binding cancer (GEJC), and histopathologically
confirmed adenocarcinoma, with at least one measurable tumor lesion (spiral CT or MR
scan =10mm, gonorrhea The short diameter of sling is =15mm, which meets the RECIST 1.1
standard); the lesion that has received radiotherapy is not selected as the target
lesion, unless the radiotherapy lesion is the only measurable lesion and is clearly
advanced according to imaging judgment, it can be considered as the target lesion;
3. Subjects have not received prior systemic therapy for locally advanced or metastatic
gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. For
subjects who have received prior neoadjuvant/adjuvant chemotherapy or
chemoradiotherapy for curative intent, the time between disease progression and last
treatment should be at least 6 months;
4. HER2 is negative. HER2 negative is defined as: IHC 0/1+, or IHC 2+ and FISH/ISH
negative (HER2: CEP17 ratio <2). FISH can be replaced by locally available and
accepted ISH methods (such as DISH);
5. The study allowed the inclusion of Subjects with gastric cancer with peritoneal
metastasis (imaging results or ascites/abdominal lavage cytology test positive);
6. Expected survival period > 3 months;
7. ECOG score: 0-1;
8. All acute toxic reactions caused by previous anti-tumor treatment or surgery are
relieved to level 0-1 (according to NCI CTCAE version 5.0) or to the level specified
in the group/exclusion standard. Except for other toxicicies that researchers such as
hair loss, fatigue and hearing damage believe do not pose a safety risk to the
subjects;
9. Have good organ function (subsists are not allowed to receive blood transfusion or
growth factor support treatment within 7 days before the first administration):
1) Absolute count of neutrophils =1.5×109/L; platelets =100×109/L; hemoglobulin =90g/L or
5.6mmol/L; 2) Total bilirubin = 1.5 times the upper limit of normal value (ULN); ALT and
AST =2.5×ULN, for liver metastasis subjects, ALT and AST =5×ULN; albumin =3.0g/dL (30g/L);
3) serum creatinine =1.5 ×ULN or calculated serum creatinine clearance =50mL/min
(Cockcroft-Gault formula calculation).
4) Normal urine routine, or urine protein <2+; if urine protein =2+, the 24-hour urine
protein quantity must be =1g; 5) Normal coagulation function, international standardization
ratio (INR) = 1.5×ULN, prothrombin time (PT) and activation partial thrombin time (APTT) =
1.5×ULN; 10. Women of childbearing age must have a negative pregnancy test (ßHCG) before
starting treatment. Women of childbearing age and men (who have sex with women of
childbearing age) must agree to use effective contraceptives continuously during treatment
and 6 months after the last therapeutic dose; 11. Subjects signed the informed consent, and
able to follow the planned visit, research treatment, laboratory examination and other
experimental procedures.
Exclusion Criteria:
1. known as squamous carcinoma, undifferentiated cancer or other tissue types of gastric
cancer, or adenocarcinoma mixed with other tissue types of gastric cancer;
2. HER2 positive stomach cancer patients: define IHC 3+, or IHC 2+ and FISH/ISH positive;
3. Previously received immune checkpoint inhibitors (such as anti-PD-1 antibodies,
anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such
as antibodies to ICOS, CD40, CD137, GITR, OX40 targets, etc.) , immune cell therapy
and other treatment of any immune mechanism for tumors;
4. In the first 14 days of randomization, there is still uncontrollable pleural hydration
and ascites after puncture drainage and other treatments. Imaging shows that a small
number of or medium chest and ascites patients can be selected for the study;
5. Subjects have not received prior systemic therapy for locally advanced or metastatic
gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. For
subjects who have received prior neoadjuvant/adjuvant chemotherapy or
chemoradiotherapy for curative intent, the time between disease progression and last
treatment should be at least 6 months;
6. There are significant clinical bleeding symptoms or clear bleeding tendencies within 1
month before the first administration, such as gastrointestinal bleeding, hemorrhagic
gastric ulcer, or vasculitis;
7. There are clinically active hemoptysis, active diverticulitis, abdominal abscess, and
gastrointestinal obstruction;
8. Any other malignant tumors have been diagnosed within 5 years before entering the
study, except for skin basal or squamous cell carcinoma, superficial bladder cancer,
cervical insitus, intraductal cancer and thyroid papilloma cancer that can be treated
locally and have been cured with clear medical records;
9. Known active or untreated brain metastases, meningeal metastases, spinal cord
compression, or leptomeningeal disease. However, subjects who meet the following
requirements and have measurable lesions outside the central nervous system are
allowed to enter the group: after treatment, the imaging is stable for at least 4
weeks before the start of the study treatment (if there is no new or expanded brain
metastasis), and systemic glucocortic hormone and anticonvulsive drug treatment has
been stopped at least 2 weeks;
10. Interstitial lung disease, non-infectious pneumonia or uncontrollable systemic
diseases (such as diabetes, hypertension, pulmonary fibrosis and acute pneumonia,
etc.) are known, and a history of active tuberculosis is known;
11. Subjects with active, known or suspected autoimmune disease. But Subjects who are in a
stable state and do not require systematic immunosuppressive treatment are allowed,
such as type 1 diabetes, hypothyroidism that only needs hormone replacement therapy,
and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis
or hair loss);
12. There are clinical symptoms or diseases of the heart that are not well controlled,
such as: (1) NYHA level 2 and above cardiac insufficiency or cardiac ultrasound
examination: LVEF (left ventricular ejection fraction) <50%; (2) severe/unstable
angina pectoris; (3) randomized myocardial infarction within 6 months ; (4) Clinically
significant supventricular or ventricular arrhythmia requires treatment or
intervention; (5) Symptomatic congestive heart failure; (6) QTc>480 ms (QTc interval
is calculated in the Fridericia formula; if QTc is abnormal, it can be separated by 2
minutes. The clock is detected 3 times in a row and takes its average value);
13. Received the following treatments or drugs before the first administration:
1. Excessive surgery within the first 28 days (tissue biopsy required for diagnosis
and peripheral vein puncture central venous catheterization [PICC] / infusion
port implantation are allowed);
2. Immunosuppressive drugs have been used within the first 14 days, excluding nasal
spray and inhalation corticosteroids or systemic steroid hormones at
physiological doses (i.e. no more than 10 mg/d prednisone or other
corticosteroids of the same physiological dose of the drug);
3. Inoculated with live attenuated vaccine within the first 28 days or within 60
days after the study period and the end of the research drug treatment;
4. Receive local anti-tumor treatment within the first 28 days (such as radiotherapy
or tumor embolization, etc.);
5. Received Chinese herbal medicine or Chinese medicine with anti-tumor indications
in the first 2 weeks;
14. Known allergies or intolerant to test drugs or their excipients; or a known history of
severe hypersensitivity reactions to other monoclon antibodies;
15. Unable to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting,
diarrhea or other gastrointestinal diseases that seriously affect drug use and
absorption;
16. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency
syndrome (AIDS), active hepatitis (hepatitis B, defined as HBV-DNA=500 IU/ml;
hepatitis C, defined as anti-HCV positive and HCV RNA higher than analysis The lower
limit of detection of the method) or combined with hepatitis B and hepatitis C;
17. Subjects who cannot comply with the test plan or cannot cooperate with the follow-up;
18. Any conditions that, in the investigator's opinion, may put subjects treated with the
study drug at risks, or interfere with the evaluation of study drug or subject safety,
or the interpretation of results.
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