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

Официальное название

A Multicenter, Randomized, Double-blind, Phase III Clinical Trial of Tislelizumab Combined With Chemotherapy Versus Placebo Plus Chemotherapy as Perioperative Treatment for MHC Class II-positive Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Обзор

Investigators has conducted a series of studies on patient selection for perioperative immunotherapy in locally advanced gastric cancer. Results from prospective single-arm trial (NCT05739045) demonstrated that 21.74% of patients achieved pathological complete response (pCR) after receiving neoadjuvant nivolumab combined with SOX regimen. Notably, investigators identified that the sensitive group exhibited upregulated MHC-II expression in malignant cells at baseline, with enriched pathways including interferon-gamma signaling and MHC class II antigen presentation. The pCR rate was significantly higher in MHC-II positive patients compared to MHC-II negative patients (36.84% vs 11.11%, P=0.038). Subsequent retrospective analyses and another prospective single-arm study focusing on MHC-II positive populations consistently showed superior short-term treatment outcomes with immunotherapy plus chemotherapy in this subgroup. Building upon these preliminary findings from small-scale studies and considering current developments in the field, we are now initiating this multicenter, randomized, double-blind, placebo-controlled phase III clinical trial. The study aims to evaluate the efficacy and safety of tislelizumab combined with chemotherapy versus placebo plus chemotherapy as perioperative treatment for MHC-II positive patients with locally advanced gastric or gastroesophageal junction adenocarcinoma.

Вмешательства

• Препарат Tislelizumab
  Received tislelizumab combined with investigator's choice of chemotherapy
• Препарат SOX or CAPOX regimen
  chemotherapy (SOX or CAPOX regimen)

Первичные конечные точки

• Pathological complete response (pCR) rates [Срок оценки: Perioperative]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• Tumors deemed unresectable due to disease extent, surgical contraindications, or patient refusal.
• Known microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors.
• History of or concurrent other malignancies (except adequately treated non-melanoma skin cancer or carcinoma in situ).
• 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).
• Presence of active ulcers, non-healing wounds, or fractures.
• Arterial/venous thrombosis within 6 months (e.g., stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism).
• Urinalysis showing ≥++ protein with confirmed 24-hour urine protein >1.0 g.
• Requiring systemic antibiotics, antivirals, or antifungals.
• Hepatitis B: HBsAg-positive with HBV DNA ≥500 IU/mL. Hepatitis C: HCV antibody-positive with HCV RNA above ULN.
• Congenital or acquired (e.g., HIV infection).
• Active autoimmune disease or history of autoimmune disease with relapse potential.
• Prior or planned organ/allogeneic bone marrow transplantation.
• Interstitial lung disease (ILD), history of steroid-treated ILD, active pneumonia on screening CT, or active tuberculosis.
• 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.
• Known allergy to any study drug or excipients.
• Currently breastfeeding.
• Any condition that, per investigator judgment, may jeopardize patient safety or study completion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital — Ханчжоу

Идентификаторы

NCT: NCT07068516 · Mountain-04

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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