Gastric or gastro-esophageal junction adenocarcinoma
Conditions
Interventions
Cohort A Experimental Group:Patients will first receive neoadjuvant SOX (S-1 and oxaliplatin) combined with trastuzumab and PD-1 inhibitor therapy, administered once every 3 weeks (Q3W). Tumor respons
Cohort A Control Group:Patients will first receive neoadjuvant SOX therapy, administered once every 3 weeks (Q3W). Tumor response assessment will be conducted after the completion of neoadjuvant thera
Cohort B:Patients will first receive neoadjuvant therapy consisting of SOX (S-1 and oxaliplatin) combined with trastuzumab and PD-1 inhibitor therapy, administered once every 3 weeks (Q3W). Tumor resp
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: Patients eligible for the study must meet all of the following criteria: 1. Have a full understanding of the study and voluntarily sign the informed consent form (ICF). 2. Histologically confirmed gastric or esophagogastric junction adenocarcinoma, clinically staged as II/III based on enhanced CT/MRI scans, i.e., staged as cT1-2N+M0 or cT3-4aNanyM0. 3. Immunohistochemistry HER2 IHC 3+ or HER2 2+ (Arm A: HER2 3+ or HER2 2+ FISH positive; Arm B: HER2 2+ FISH negative or HER2 IHC 1+ & FISH positive). 4. Agree to provide either archived tumor tissue specimens or undergo biopsy to collect tumor tissue for PD-L1, EBV, and MSI immunohistochemistry (IHC) testing at the central laboratory. 5. Age between 18 and 80 years, regardless of gender. 6. Good general condition, with an ECOG score of 0-1 and no surgical contraindications. 7. Adequate physical condition and organ function to undergo major abdominal surgery. 8. Expected survival period = 3 months. 9. Laboratory values within the following criteria within 7 days before enrollment: a. WBC > 4.0×10^9/L and 1.5×10^9/L, Hb = 90g/L, PLT = 100×10^9/L. b. Serum bilirubin = 1.5× upper limit of normal (ULN), AST, ALT = 2.5× ULN. c. Creatinine = 1.5× ULN or serum clearance rate > 60ml/min, estimated glomerular filtration rate according to Cockcroft-Gault formula: (140 - age) × (weight, kg) × (0.85 for females)/72 × (serum creatinine, mg/dL) or: (140 - age) × (weight, kg) × (0.85 for females)/0.818 × (serum creatinine, µmol/L). d. INR and aPTT = 1.5 × ULN, applicable only for subjects not receiving anticoagulant therapy; subjects receiving anticoagulant therapy should be on stable doses. 10. Good compliance and willingness to cooperate with laboratory tests, auxiliary examinations, and corresponding specimen collection according to the protocol. 11. Women of childbearing potential (including those who are postmenopausal due to chemical menopause or other medical reasons) must agree to use contraception from the signing of the informed consent form until at least 5 months after the last dose of study treatment or adjuvant chemotherapy (whichever is later). Women must also agree not to breastfeed during this period. Men must agree to use contraception from the administration of the investigational drug until at least 7 months after the last dose of investigational drug or adjuvant chemotherapy (whichever is later).
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria must not be enrolled: 1. Known allergy to any component of the investigational drugs, including monohydrate citric acid, sodium dihydrate citrate, mannitol, and polysorbate. 2. Previous or concurrent malignancies, except for completely excised basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, mucosal carcinoma, superficial bladder carcinoma, or any other cancer without recurrence for at least 5 years. 3. Uncontrollable pericardial effusion, pleural effusion, ascites, gastrointestinal bleeding, or high-risk bleeding within 2 weeks before enrollment. 4. Weight loss exceeding 20% within 2 weeks before enrollment. 5. Inability to take oral medications. 6. History of chemotherapy, radiotherapy, immunotherapy, or gastric cancer surgery. 7. Previous use of anti-HER2, anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, or anti-CTLA-4 antibody (or any other antibody acting on T cell co-stimulation or checkpoint pathways). 8. Receipt of tyrosine kinase inhibitor therapy within 2 weeks before enrollment. 9. Complications requiring long-term use of immunosuppressive drugs or requiring systemic or local administration of corticosteroids with immunosuppressive doses (> 10mg/day of prednisone or equivalent) before enrollment. 10. Vaccination with any anti-infective vaccines (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks before enrollment. 11. Uncontrolled diabetes, hypertension, or other systemic diseases. 12. Receiving or requiring anticoagulant therapy (excluding low-dose aspirin antiplatelet therapy). 13. Active autoimmune diseases or history of autoimmune diseases (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or childhood asthma completely relieved, and no intervention required in adulthood may be included; subjects with asthma requiring bronchodilators for medical intervention in adulthood cannot be included). 14. Active pulmonary tuberculosis (TB), undergoing anti-tuberculosis treatment, or having received anti-tuberculosis treatment within 1 year before screening. 15. History of the following pulmonary diseases confirmed by imaging (preferably CT) or clinical results: interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis, acute pulmonary diseases. 16. Contraindications to oxaliplatin or tegafur. 17. Pregnant or lactating women or women of childbearing potential. 18. No active hepatitis. 19. Positive results for any of the following tests: human immunodeficiency virus-1 (HIV-1) antibody, human immunodeficiency virus-2 (HIV-2) antibody, human T-lymphotropic virus-1 (HTLV-1) antibody, hepatitis C virus (HCV) antibody. 20. Any other clinically significant diseases or conditions that investigators believe may affect protocol compliance, affect subjects' signing of informed consent forms (ICFs), or are not suitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Pathological Response, pCR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Major Pathological Response, MPR;Tumor Regression Grade 0/1, TRG 0/1;R0 Resection Rate;Relapse-Free Survival, RFS;Event-Free Survival, EFS;Overall Survival, OS;Safety;Quality of Life; | — |
Countries
China
Contacts
Public ContactYuanfang Li; Shuming Yuan; Yongming Chen
Sun Yat-Sen University Cancer Center
Outcome results
None listed