Neoadjuvant Tislelizumab + LM-302 + S-1 or Tislelizumab + SOX for CLDN18.2-Positive Gastric/GEJ Adenocarcinoma

Tislelizumab Combined With LM-302 and S-1 Versus Tislelizumab Combined With SOX for Neoadjuvant Treatment of Claudin 18.2-positive Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a Prospective, Randomized, Exploratory Study

In this study, the investigators will use Tislelizumab combined with LM-302 and S-1 versus Tislelizumab combined with SOX to treat Claudin 18.2-positive locally advanced gastric or gastroesophageal junction adenocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Gastric or Esophagogastric Junction Adenocarcinoma
• Intervention / Treatment: Drug: Tislelizumab, LM-302 and S-1; Drug: Tislelizumab combined with oxaliplatin and S-1

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhongyin Yang; Phone Number: 8621-64370045; Email: jeffreyyong@163.com

Study Locations

• China
  • Huangpu District
    • Shanghai, Huangpu District, China, 200025
      • Recruiting
      • Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients voluntarily participate in this study and sign the informed consent form;
• Age ≥ 18 years;
• Histopathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma;
• HER2 negative;
• Determined by contrast-enhanced CT and laparoscopy to have radically resectable disease with clinical stage T3-4 N+ M0 (according to the AJCC 8th edition);
• Claudin 18.2 positive (≥25% of tumor cells showing moderate-to-strong membrane staining);
• No prior receipt of other targeted therapies against claudin 18.2;
• ECOG performance status 0-1;
• Life expectancy ≥ 12 months;
• Adequate major organ function.

Exclusion Criteria:

• Known HER2-positive gastric cancer；
• Gastroesophageal junction (EGJ) cancer involving the proximal stomach with the tumor center located ≤2 cm from the EGJ；
• Peritoneal metastasis, positive peritoneal cytology (CY1P0), or retroperitoneal lymph node metastasis (No. 16a2/b1) or other distant metastases;
• Presence of unresectable factors, including unresectability due to tumor characteristics, surgical contraindications, or patient refusal of surgery;
• Prior or concurrent other malignancy, except for cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and carcinoma in situ of the breast;

• Presence of any of the following cardiac clinical symptoms or diseases:

  • New York Heart Association (NYHA) class ≥2 heart failure or left ventricular ejection fraction (LVEF) <50% on color Doppler echocardiography;
  • Unstable angina;
  • Resting electrocardiogram (ECG) showing QTc >450 ms (male) or QTc >470 ms (female);
  • Resting ECG showing clinically significant abnormalities (e.g., abnormalities in heart rate, conduction, morphology), complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, or PR interval >250 ms.
• History of gastrointestinal perforation, intra-abdominal abscess, or intestinal obstruction within the past 3 months, or evidence of intestinal obstruction by imaging or clinical symptoms;
• Arterial/venous thrombotic events within 6 months before randomization, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, or pulmonary embolism;
• Known hereditary or acquired bleeding or thrombotic predisposition (e.g., hemophilia, coagulation disorders, thrombocytopenia);
• Active peptic ulcer, unhealed wound, or bone fracture;
• Active infection requiring antimicrobial therapy (e.g., antibacterial, antiviral, or antifungal treatment);
• Active hepatitis [hepatitis B: HBsAg positive and HBV DNA ≥500 IU/mL; hepatitis C: HCV antibody positive and HCV viral load > upper limit of normal]; 13. Congenital or acquired immunodeficiency (e.g., HIV-infected patients);
• Planned or prior organ or allogeneic bone marrow transplantation;
• Current interstitial pneumonia or interstitial lung disease, or a history of interstitial pneumonia/ lung disease requiring steroid therapy, or other pulmonary conditions that may interfere with the assessment and management of immune-related lung toxicity, including pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), pneumoconiosis, drug-induced pneumonitis, idiopathic pneumonitis, or active pneumonia or severe pulmonary dysfunction on screening CT scan;
• Active pulmonary tuberculosis;
• Any active autoimmune disease or history of autoimmune disease with potential for relapse [including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (patients controlled with hormone replacement therapy alone are eligible)];
• Known hypersensitivity to any study drug or excipient;
• Lactating women;
• Any other condition that, in the investigator's judgment, may affect the study results or necessitate premature termination of the study, such as alcohol or drug abuse, other serious diseases (including psychiatric disorders) requiring concomitant treatment, significant laboratory abnormalities, or family/social factors that could compromise patient safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab Combined With LM-302 and S-1	Drug: Tislelizumab, LM-302 and S-1; Tislelizumab 200mg and LM-302 2.0mg/kg intravenous (IV) infusion on day 1 plus oral S-1: BSA<1.25 m2, 40mg twice/day; BSA1.25-1.5m2, 50mg twice/day; BSA≥1.5 m2, 60mg twice/day, po, d1-14, q3w.
Active Comparator: Tislelizumab Combined With SOX	Drug: Tislelizumab combined with oxaliplatin and S-1; Tislelizumab 200mg and oxaliplatin 130 mg/m2 intravenous (IV) infusion on day 1 plus oral S-1: BSA<1.25 m2, 40mg twice/day; BSA1.25-1.5m2, 50mg twice/day; BSA≥1.5 m2, 60mg twice/day, po, d1-14, q3w.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response (pCR) rate	pCR is defined as the absence of residual tumor based on evaluation of the resected stomach and lymph node specimen according to Becker remission criteria	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment related adverse events		up to 24 months
Major Pathological Response (MPR) rate	Defined as tumor specimens resected after neoadjuvant therapy with residual tumor cells ≤10%	up to 24 months
R0 resection rate	R0 resection rate was defined as the proportion of patients with complete resection of the tumor and negative margins, i.e. no residual tumors	up to 24 months
Event-free survival (EFS)	Event-free survival (EFS) is defined as the time from treatment initiation until the occurrence of any predefined event, including disease progression preventing planned surgery, local or distant recurrence, or death from any cause	up to 36 months
Overall survival (OS)	Overall survival (OS) is defined as the period from the initial date of neoadjuvant therapy to the date of death due to any cause.	up to 36 months
treatment related adverse events	It is defined according to the AJCC 8th edition ypN staging system, with the ypN0 rate and total number of positive lymph nodes in the two groups.	up to 24 months

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: May 1, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Tislelizumab; SOX; Claudin 18.2; Gastric or Esophagogastric Junction Adenocarcinoma; LM-302
• Additional Relevant MeSH Terms: Organic Chemicals; Coordination Complexes; Oxaliplatin; tislelizumab; S 1 (combination)
• Other Study ID Numbers: DRAGON-18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No