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

NCT07068516 | Not Yet Recruiting Phase 3

• 1 other identifier: Mountain-04
• Study Type: interventional
• Target: 470
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Cancer Stage

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rates

  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 .

  Perioperative

Study Arms (2)

Chemotherapy

PLACEBO COMPARATOR

Received placebo combined with investigator's choice of chemotherapy (either SOX or CAPOX regimen

Drug: SOX or CAPOX regimen

Chemotherapy and immunotherapy

EXPERIMENTAL

Received tislelizumab combined with investigator's choice of chemotherapy (SOX or CAPOX regimen

Drug: Tislelizumab; Drug: SOX or CAPOX regimen

Interventions

Tislelizumab DRUG

Received tislelizumab combined with investigator's choice of chemotherapy

Chemotherapy and immunotherapy

SOX or CAPOX regimen DRUG

chemotherapy (SOX or CAPOX regimen)

Chemotherapy; Chemotherapy and immunotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Xiangdong Cheng: lead
• Sichuan Cancer Hospital and Research Institute: collaborator
• Liaoning Cancer Hospital & Institute: collaborator

Study Sites (1)

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Interventions

tislelizumab; XELOX

Central Study Contacts

Xiangdong Cheng

CONTACT

0086-571-881280; Chengxd516@126.com

Can Hu

CONTACT

13968032995; chengxd@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 15, 2025
• First Posted: July 16, 2025
• Study Start: July 20, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2030
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)