Iparomlimab and Tuvonralimab Injection (QL1706) Combined With DOS as Neoadjuvant Therapy for Locally Advanced Adenocarcinoma of the Stomach and Gastroesophageal Junction

Inclusion criteria

• Aged 18-75 years old, male or female;
• Previously untreated, surgically resectable adenocarcinoma of the stomach or gastroesophageal junction;
• Clinical stage cT3-4a/N+M0;
• ECOG performance status 0-1;
• Adequate function of major organs assessed within 7 days before treatment:

• Hematological indicators (without blood transfusion within 14 days):

Hemoglobin (HB) ≥90 g/L; Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Platelet (PLT) ≥80×10⁹/L;

• Biochemical indicators:

Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance (CCr) ≥60 ml/min;

• Assessed by Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%);
• Thyroid function: thyroid stimulating hormone (TSH) ≤ ULN;
• Subjects of childbearing potential agree to use effective contraception during the study and for 6 months after the end of study treatment;
• Subjects voluntarily participate in this study and sign written informed consent.

Exclusion criteria

• Inclusion Criteria:
• Aged 18-75 years old, male or female;
• Previously untreated, surgically resectable adenocarcinoma of the stomach or gastroesophageal junction;
• Clinical stage cT3-4a/N+M0;
• ECOG performance status 0-1;
• Adequate function of major organs assessed within 7 days before treatment:

• Hematological indicators (without blood transfusion within 14 days):

Hemoglobin (HB) ≥90 g/L; Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Platelet (PLT) ≥80×10⁹/L;

• Biochemical indicators:

Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance (CCr) ≥60 ml/min;

• Assessed by Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%);
• Thyroid function: thyroid stimulating hormone (TSH) ≤ ULN;
• Subjects of childbearing potential agree to use effective contraception during the study and for 6 months after the end of study treatment;
• Subjects voluntarily participate in this study and sign written informed consent.

Exclusion criteria

• History of hypersensitivity to any component of QL1706, tegafur-gimeracil-oteracil potassium, oxaliplatin, docetaxel, or any of their excipients;
• History of other malignant tumors within the past 5 years or concurrent other malignant tumors, except cured carcinoma in situ of cervix, non-melanoma skin cancer, and superficial bladder tumors;
• Patients with distant metastasis or unresectable disease;
• Prior receipt of immunotherapy (anti-PD-1, anti-PD-L1, anti-CTLA-4, etc.);
• Received any anti-tumor agents within 4 weeks prior to the first study drug administration;
• Patients with intestinal obstruction (including incomplete intestinal obstruction) or other gastrointestinal diseases that may lead to gastrointestinal hemorrhage, perforation or obstruction;
• Patients with any bleeding event ≥ CTCAE Grade 3, unhealed wounds, ulcers or fractures within 4 weeks before screening;
• Concurrent enrollment in another interventional clinical trial, except observational (non-interventional) clinical trials or follow-up phase of interventional trials;
• Subjects requiring systemic treatment with corticosteroids (>10 mg prednisone equivalent daily) or other immunosuppressants within 2 weeks before the first study drug administration;
• Received live vaccines within 4 weeks prior to the first study drug administration;
• Underwent major surgery or suffered trauma within 4 weeks before the first study drug administration;
• Active autoimmune disease or history of autoimmune disease, except vitiligo or childhood asthma/allergy that has resolved and requires no intervention in adulthood;
• History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, or history of organ transplantation and allogeneic bone marrow transplantation;
• Subjects with inadequately controlled cardiovascular clinical symptoms or diseases;
• Severe infection (CTCAE Grade > 2) occurring within 4 weeks prior to the first study drug administration;
• History of interstitial lung disease (except radiation pneumonia without corticosteroid treatment), non-infectious pneumonia, active pulmonary tuberculosis infection; patients with history of active pulmonary tuberculosis infection within 1 year before enrollment, or patients with history of active pulmonary tuberculosis infection more than 1 year ago without standardized treatment;
• Pregnant or breastfeeding women;
• Other concomitant diseases that, in the investigator's opinion, may seriously endanger the subject's safety or prevent the subject from completing the study.