For locally advanced esophagogastric junction and gastric cancer, neoadjuvant chemotherapy can downstage T and N stage,treated distant micrometastases early , and finally improve the long-term survival. Combination of perioperative PD-1 antibody and chemotherapy for locally advanced esophagogastric junction and gastric cancer could be a novel therapy to increase response rate and reduce recurrence rate.Cadonilimab, a tetravalent bispecific antibody targeting PD-1 and CTLA-4, is designed to retain the efficacy benefit of combination of PD-1 and CTLA-4 and improve on the safety profile of the combination therapy. The aim of this study is to evaluate the efficacy and safety of cadonilimab Plus Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer.

Locally advanced esophagogastric junction and gastric cancer could be cured by multi-disciplinary therapies including surgery, chemotherapy and radiotherapy. Neoadjuvant chemotherapy can downstage T and N stage, treated distant micrometastases early before local therapy has begun, and finally improve the long-term survival. However, the therapeutic effects remain unsatisfactory.Cadonilimab (AK104), a novel bispecific antibody simultaneously targeting PD-1 and CTLA-4, was designed to boost anti-tumor activity with a favorable safety profile.This study was a single arm, open-label clinical study to evaluate the efficacy and safety of combination with Cadonilimab and Chemotherapy for neoadjuvant treatment of resectable locally advanced adenocarcinoma of the gastro-esophageal junction.

Key Inclusion Criteria:

1. Confirmed gastric and gastroesophageal junction adenocarcinoma by Gastroscopic biopsy histopathological examination.
2. Imaging (CT/MRI) and diagnostic laparoscopy confirmed at the stage of cT3-4aN1-3M0(AJCC 8th) .
3. Physical condition and organ function allow for for larger abdominal surgery.
4. Adequate haematological, renal and liver function.

Key Exclusion Criteria:

1. Patients who have HER2 positive confiemed with IHC3+ or IHC2+ and FISH positive.
2. Confirmed at stage IV (AJCC 8th) or unresectable by investigator.
3. Prior chemotherapy, radiotherapy, surgery immunotherapy or molecular targeted therapy for gastric cancer.
4. Patients are allergic to study medication and its ingredients.
5. Known active autoimmune diseases.
6. Presence of other uncontrolled serious medical conditions.