PD-1 Blockade With JS001 Plus Neoadjuvant Chemotherapy for Gastric/Gastroesophageal Junction Cancer

Prior treatment

• Patients have received prior therapy with anti-PD-1, anti-PD-L1 or anti-CTLA4 agent.
• Patients with history of autoimmune disease; patients with autoimmune-related hypothyroidism receive stable doses of thyroid hormone replacement therapy Eligible to participate in this study; Type 1 diabetes patients who are controlled after receiving a stable insulin treatment plan are eligible to participate in this study;
• Patients have received systemic immunostimulatory drug therapy (including but not limited to interferon or IL-2) within 4 weeks before enrollment or within 5 half-lives of the drug (whichever is shorter);
• Patients who have undergone allogeneic bone marrow transplantation or solid organ transplantation in the past;
• Patients with previous or cured HBV infection (defined as hepatitis B core antibody \[anti-HBc\] positive and HbsAg negative) are only eligible to participate in this study when HBV DNA is negative (HBV DNA ˂1000cps/ml).
• Major cardiovascular diseases, such as New York Heart Association heart disease (level II or higher), myocardial infarction within 3 months before randomization, unstable arrhythmia, or unstable angina.

Other illness

• Patients with a history of severe hypersensitivity to other monoclonal antibodies or any component of toripalimab injection (JS001).
• Patients have experienced or currently have other malignancies within 5 years.
• Active infections, including tuberculosis (clinical diagnosis includes clinical history, physical examination and imaging findings, and TB examination according to local medical routines), hepatitis B {known HBV surface antigen (HBsAg) positive, and HBV DNA ≥1000cps/ml}, hepatitis C or human immunodeficiency virus (HIV antibody positive).
• Patients with positive hepatitis C (HCV) antibodies are only eligible to participate in this study if the polymerase chain reaction shows negative HCV RNA.
• There is a serious neurological or mental illness, including dementia and seizures.
• Chronic bowel disease or short bowel syndrome.

Lab values

• Patients with known coronary artery disease, congestive heart failure that does not meet the above criteria, or left ventricular ejection fraction \<50% must adopt an optimized and stable medical plan determined by the treating doctor. If necessary, you can consult a cardiologist.

Other

• Preoperative pathology diagnosed as squamous cell carcinoma or neuroendocrine tumor.
• Suffer from NCI-CTCAE ≥ Grade 2 peripheral neuropathy.
• Women who are pregnant or breastfeeding.
• Those who are deficient in the enzyme dihydropyrimidine dehydrogenase (DPD).

• Age ≥18 yeas and ≤79 years. The gender is not limited.
• Confirmed gastric and gastroesophageal junction adenocarcinoma by Gastroscopic biopsy histopathological examination.
• Endoscopic ultrasonography and/or enhanced CT/MRI examination confirmed at the stage of cT3/4a Nx or T2 N1-3, M0(AJCC 8th) before randomization.
• At least 15 unstained sections of formalin-fixed paraffin-embedded tumor tissue sections or fresh tumor tissues can be provided for PD-L1, TMB, tumor infiltrating T lymphocytes, MSI-H/dMMR and EBV detection.
• The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1
• Adequate bone marrow and organ function meets the following criteria:
  • Neutrophil count (ANC)≥1.5×l09/L
  • Platelet (PLT) ≥80×109/L
  • Hemoglobin (Hb) level ≥9.0 g/L
  • Total bilirubin level≤1.5×ULN
  • Alanine aminotransferase (ALT) level≤3×ULN
  • Aspartate aminotransferase (AST) level ≤3×ULN
  • International normalized value (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5×ULN
  • Serum creatinine (Cr) level ≤1.5×ULN
  • Creatinine clearance \>50 ml/min (Calculated according to the Cockcroft-Gault formula)