Perioperative Tislelizumab Plus Chemotherapy Versus Chemotherapy Alone in MHC-II-Positive Gastric/GEJ Cancer

Korábbi kezelés

• History of or concurrent other malignancies (except adequately treated non-melanoma skin cancer or carcinoma in situ).
• Prior or planned organ/allogeneic bone marrow transplantation.
• Current or recent use of immunosuppressants or systemic corticosteroids (except physiologic replacement doses).
• Received live attenuated vaccines within 28 days before treatment or requiring them during/within 60 days post-treatment.

Más betegség

• Tumors deemed unresectable due to disease extent, surgical contraindications, or patient refusal.
• Chronic or clinically significant conditions that may compromise treatment tolerance (e.g., severe cardiac disease, uncontrolled hypertension, significant hepatic/renal dysfunction).
• History of gastrointestinal perforation, intra-abdominal abscess, or bowel obstruction within 3 months (or clinical/radiologic suspicion of obstruction).
• Arterial/venous thrombosis within 6 months (e.g., stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism).
• Congenital or acquired (e.g., HIV infection).
• Active autoimmune disease or history of autoimmune disease with relapse potential.
• Interstitial lung disease (ILD), history of steroid-treated ILD, active pneumonia on screening CT, or active tuberculosis.
• Known allergy to any study drug or excipients.
• Any condition that, per investigator judgment, may jeopardize patient safety or study completion.

Laborértékek

• Hepatitis B: HBsAg-positive with HBV DNA ≥500 IU/mL. Hepatitis C: HCV antibody-positive with HCV RNA above ULN.

Egyéb

• Known microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors.
• Presence of active ulcers, non-healing wounds, or fractures.
• Urinalysis showing ≥++ protein with confirmed 24-hour urine protein \>1.0 g.
• Requiring systemic antibiotics, antivirals, or antifungals.
• Currently breastfeeding.

• Willingness to participate and signed informed consent form
• ≥18 years old
• Histologically confirmed gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma
• MHC-II immunohistochemistry (IHC) 2+/3+
• Locally advanced disease (cT3-4a, N+, M0) confirmed by CT and/or diagnostic laparoscopy (AJCC 8th edition)
• No previous anticancer therapy (surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.)
• Scheduled to undergo curative resection after neoadjuvant therapy
• Ability to swallow oral medication
• ECOG performance status 0-1
• Estimated survival ≥6 months
• Hematological (without transfusion/G-CSF support within 14 days):ANC ≥1.5×10⁹/, Platelets ≥80×10⁹/L, Hemoglobin ≥80 g/L. Hepatic/Renal: Total bilirubin \<1.5×ULN, ALT/AST ≤2.5×ULN, Serum creatinine ≤1.5×ULN or CrCl \>50 mL/min (calculated by Cockcroft-Gault formula: Male: CrCl = \[(140-age) × weight (kg)\] / (72 × serum Cr \[mg/dL\]), Female: CrCl = \[(140-age) × weight (kg)\] / (72 × serum Cr \[mg/dL\]) × 0.85.
• Contraception Requirements: Female participants of childbearing potential: Negative serum pregnancy test within 7 days before enrollment; agreement to use highly effective contraception during treatment and for 120 days after last dose. Female participants of childbearing potential: Negative serum pregnancy test within 7 days before enrollment; agreement to use highly effective contraception during treatment and for 120 days after last dose.