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

Not Applicable

Not yet recruiting

• Conditions: Gastric Cancer Stage
• Interventions: Drug: SOX or CAPOX regimen; Drug: Tislelizumab

• Registration Number: NCT07068516
• Lead Sponsor: Xiangdong Cheng

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-06-15
• Status Verified: 2025-07
• Study First Submitted QC: 2025-07-06
• Last Update Submitted: 2025-07-06
• Study First Posted: 2025-07-16
• Last Update Posted: 2025-07-16
• Study Start: 2025-07-20
• Primary Completion: 2027-06-30
• Study Completion: 2030-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 470

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy	SOX or CAPOX regimen	Received placebo combined with investigator's choice of chemotherapy (either SOX or CAPOX regimen
Chemotherapy and immunotherapy	Tislelizumab	Received tislelizumab combined with investigator's choice of chemotherapy (SOX or CAPOX regimen
Chemotherapy and immunotherapy	SOX or CAPOX regimen	Received tislelizumab combined with investigator's choice of chemotherapy (SOX or CAPOX regimen

Primary Outcome Measures

Name	Time	Method
Pathological complete response (pCR) rates	Perioperative	To compare the pathological complete response (pCR) rates between tislelizumab plus chemotherapy and placebo plus chemotherapy as perioperative therapy for MHC-II-positive locally advanced gastric or gastroesophageal junction adenocarcinoma .

Trial Locations

Locations (1)

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital); 🇨🇳 Hangzhou, Zhejiang, China