Gastric cancer is one of the most common malignancies in China with incidence and mortality
both ranking the 2nd among malignancies in China. Surgery is the only possible way to cure
gastric cancer, however, over 80-90% of gastric cancer patients in China are in advanced
stage. Locally advanced gastric cancer could be cured by multi-disciplinary therapies
including surgery, chemotherapy and radiotherapy. Neoadjuvant chemotherapy can increase the
resectability of tumor, and finally improve the long-term survival. However, the therapeutic
effects remain unsatisfactory.
Combination of perioperative PD-1 antibody and chemotherapy for locally advanced gastric
cancer could be a novel therapy to increase response rate and resectability and reduce
recurrence rate. Camrelizumab in this study is a Chinese anti-PD-1 monoclonal antibody for
injection which has been approved for melanoma and Hepatocellular carcinoma .This study is a
single center, open-label, randomized comparative phase II clinical trial to evaluate safety
and efficacy of Camrelizumab in combination with perioperative chemotherapy in locally
advanced adenocarcinoma of stomach or gastroesophageal junction. Differences in T cell
expression were detected by single cell RNA sequencing to screen people who were more
sensitive to immunotherapy.
Inclusion Criteria:
1. Written (signed) informed consent.
2. Age ≥ 18 years and ≤70 years.
3. ECOG Performance status 0-1.
4. Has previously untreated localized gastric or gastroesophageal junction adenocarcinoma
as defined by T3 or greater primary lesion or the presence of any positive nodes - N+
(clinical nodes) without evidence of metastatic disease.
5. Patients who plan surgery after neoadjuvant chemotherapy based on clinical staging
criteria.
6. Consent to send tumor tissue from biopsy or resection for PD-L1 detection and PD-L1
CPS≥1;
7. Expected survival ≥6 months;
8. Females of child bearing age must have a negative pregnancy test
9. 1）Platelet (PLT) ≥100×109/L; 2) Neutrophil count (ANC)≥1.5×l09/L; 3) Hemoglobin (Hb)
level ≥9.0 g/dl; 4）WBC≥3.5×l09/L; 5) International normalized ratio (INR) ≤1.5; 5)
Prothrombin time (PT) ,International Normalized Ratio（INR）and activated partial
thromboplastin time (APTT) ≤1.5×ULN; 6）Total bilirubin (TBIL) level ≤1.5×ULN（patients
with gilbert syndrome≤3×ULN）; 7) Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) level ≤2.5×ULN ; 10) Serum creatinine (Cr) level ≤1.5×ULN and
creatinine clearance ≥60 ml/min;
Exclusion Criteria:
1. Patients with pathologically confirmed gastric squamous cell carcinoma, adenosquamous
carcinoma, small cell carcinoma, and undifferentiated gastric cancer.
2. patients who have HER2 positive confiemed with IHC3+ or IHC2+ and FISH positive.
3. Patients with a history of t Anticancer or Experimental Therapy(Including
chemotherapy, radiotherapy, hormone therapy and molecular targeted therapy)
4. The patient's cardia or pylorus is nearly obstructed, affecting eating and gastric
emptying
5. Immunotherapy with previous anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or
anti-CTLA-4 antibodies or any other antibody or drug that targets T-cell
co-stimulation or immune checkpoint pathways
6. Patients have experienced or currently has other malignancies within 5 years.Except
for the cured cervical carcinoma in situ,Non-melanoma skin cancer, Other tumors or
cancers that have been treated radically and have shown no signs of disease for at
least 5 years.
7. Peripheral neuropathy ≥ level 2（according to CTCAE 5.0）
8. Patient currently has CNS or cancerous meningitis.
9. Patients are allergic to study medication and its ingredients
10. Patients have hereditary bleeding or coagulopathy at risk of bleeding
11. Patient underwent major surgery within 4 weeks
12. Patients have taken Chinese herbal medicine or proprietary Chinese medicine for cancer
treatment within two weeks
13. Patients have not recovered from complications of previous surgery.According to the
CTCAE 5.0, it has not been reduced below level 1(In addition to hair loss and fatigue)
14. Patients require immunosuppressive drugs within 2 weeks or less or during the
study.Exclude the following:
A) Use of intranasal, inhaled or topical steroid(For example, intra - articular
injection) B) physiological dose of steroid ( Prednisone less than 10mg per day or use
equivalent dose) C) Short-term(no more than 7 day) use of steroids to prevent or treat
non-autoimmune allergic diseases
15. Patients have an active or history of autoimmune disease that may recur
16. Patients have a history of interstitial lung disease or non-infectious pneumonia
17. Patients have a history of active tuberculosis
18. Patients have a history of HIV infection or other acquired, congenital
immunodeficiency disease , organ transplant or stem cell transplant
19. Hepatitis B or C virus virological tests meet any of the following:
A) HBsAg positive ,HBV-DNA≥150 copies/mL or ≥2000IU/mL B) HCV antibody positive and
HCV-RNA is above the detection limit of the analysis method
20. Within 2 weeks or 2 weeks before randomization,Patients have an active or
uncontrollable infection that requires systemic treatment
21. Patient vaccinated with live virus within 4 weeks
22. Patients have uncontrollable pleural effusion, pericardial effusion, or ascites
requiring repeated drainage or treatment.
23. Patients have gastrointestinal perforation or fistula within 6 months and significant
clinically significant gastrointestinal bleeding before 3 months of randomization
24. Patient have intestinal obstruction, inflammatory bowel disease, extensive bowel
resection, Crohn's disease, ulcerative colitis or chronic diarrhea
25. Patients have serious internal medicine diseases
26. Women who are pregnant, breast-feeding or planning to become pregnant during treatment
or within 6 months after treatment ends.
27. Patients are unwilling to receive effective contraception during treatment and within
6 months after treatment ends
28. The investigator believes that the subject is not suitable for the study
