A Study of Cadonilimab Combined with Chemotherapy in Treating Patients with Gastric or Gastroesophageal Junction Cancer

Inclusion Criteria

• Capable of providing signed informed consent
• Age >= 18 years at time of informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment
• Pathologically confirmed gastric or GEJ adenocarcinoma with T1 N+ M0 or T2-4 N0-3 M0 (per American Joint Committee on Cancer [AJCC] 8th edition) resectable disease deemed eligible for radical surgery. A diagnostic laparoscopy is strongly recommended to confirm M0 status
• HER2-negative tumor (immunohistochemistry [IHC] 0, 1+, or IHC 2+ and fluorescence in situ hybridization [FISH] non-amplified)
• Hemoglobin >= 9.0 g/dL
• Absolute neutrophil count >= 1.5 x 10^9/L
• Platelet count >= 100 x 10^9/L
• Serum bilirubin =< 1.5 x upper limit of normal (ULN). Patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
• Albumin >= 2.8g/dL (albumin infusion is not allowed within 14 days before the start of treatment)
• Measured creatinine clearance > 50 mL/min as determined by Cockcroft-Gault using actual body weight
• Willing and able to undergo pre-treatment (during screening) and on-treatment tumor biopsies
• Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose and agree to take effective contraception measures during the study drug administration and within 9 months after the last dose
• Male patients with female partners of childbearing potential must agree to take effective contraception measures during the study drug administration and within 6 months after the last dose

Exclusion Criteria

• Histologies other than adenocarcinoma, including squamous/adenosquamous cell carcinoma, neuroendocrine, or gastrointestinal (GI) stromal tumor
• HER2-positive tumor (IHC 2+ and FISH-amplified, or IHC 3+)
• Prior anticancer treatment for the disease under study (chemotherapy, radiation therapy, chemoradiation, approved or investigational therapy) prior to initiation of study treatment
• Prior receipt of an anti-PD1 or anti-CTLA4 monoclonal antibody, including for prior non-gastric malignancy
• Underlying medical conditions that, in the investigator’s opinion, make the administration of cadonilimab hazardous, including but not limited to: * Interstitial lung disease (ILD), including history of ILD or non-infectious pneumonitis * Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of initiation of cadonilimab with the exception of prophylactic antibiotic treatment * Clinically significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease or cerebrovascular accident within 3 months prior to initiation of study treatment, myocardial infarction within 6 months prior to initiation of study treatment, or unstable arrhythmia * A condition or unresolved AE from a prior investigational drug that may obscure interpretation of toxicity determination or AEs * History of prior solid-organ transplant, including allogeneic bone marrow transplant
• Concurrent chronic medical condition requiring the use of supraphysiologic doses of corticosteroids (> 10 mg/day of oral prednisone or equivalent) or immunosuppressive medications (absorbable topical corticosteroids not excluded)
• Any active autoimmune disease or documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (i.e. with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma or atopy * Replacement therapy (e.g. insulin, levothyroxine) is not considered a form of systemic treatment * Participants with asthma who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections not excluded * Participants with hypothyroidism stable on hormone replacement or Sjogren’s syndrome not excluded
• Known hypersensitivity to any excipient contained in the formulations of study interventions
• Prior active malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer(s), superficial bladder cancer, or carcinoma in-situ of the cervix, breast, or prostate cancer. Other cases of prior malignanices may be allowed after discussion with the principal investigator
• Known HIV infection with detectable viral load. Patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Known acute hepatitis B or chronic hepatitis B infection with active untreated disease. For patients with evidence of chronic infection, the hepatitis B virus (HBV) viral load must be undetectable on suppressive therapy, if indicated
• Known hepatitis C infection with detectable viral ribonucleic acid (RNA). Patients with hepatitis C virus (HCV) infection who are currently on treatment are eligible if they have an undetectable HCV viral load
• Receipt of a live attenuated vaccine within 30 days of study treatment initiation