Overview

In this study, the investigators will use LM-302 and S-1 plus intraperitoneal paclitaxel with or without Cadonilimab to treat Claudin 18.2-positive gastric or gastroesophageal junction adenocarcinoma with peritoneal metastasis.

Eligibility

Inclusion Criteria:

• Histologically confirmed gastric or gastroesophageal junction adenocarcinoma with her 2 (-), and without the history of resection of primary or metastatic lesion;
• Age ≥ 18 years at registration;
• Peritoneal metastases from gastric cancer requiring definitive diagnosisby laparoscopy, and without gastric outflow tract obstruction andintestinal obstruction;
• Claudin 18.2 positive (≥ 25%, moderate to strong staining);
• Eastern Cooperative Oncology Group (ECOG) score ≤ 1;
• Expected life expectancy \> 3 months;
• Adequate bone marrow, liver, and renal functions.

Exclusion Criteria:

• Presence of distant metastases other than peritoneal metastasis at the time of enrollment;
• Pregnant or breastfeeding women;
• Prior treatment with Claudin 18.2 targeted therapy;
• History of other malignancies within the past 5 years, except for cured skin cancer or cervical carcinoma in situ;
• History of uncontrolled epilepsy, central nervous system disease, or mental disorder that, in the investigator's judgment, may interfere with signing informed consent or compliance with oral medication.
• Clinically significant active heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or higher congestive heart failure, severe arrhythmia requiring medication, or myocardial infarction within the past 12 months;
• Upper gastrointestinal obstruction, abnormal physiological function, or malabsorption syndrome that may affect S 1 absorption;
• Known peripheral neuropathy ≥ NCI CTC AE grade 1. However, patients with loss of deep tendon reflexes (DTR) alone may be included;
• Organ transplantation requiring immunosuppressive therapy;
• Severe uncontrolled recurrent infection or other severe uncontrolled concomitant diseases;
• Moderate or severe renal impairment (creatinine clearance ≤ 50 ml/min) or serum creatinine above the upper limit of normal;
• Known dihydropyrimidine dehydrogenase (DPD) deficiency;
• Active hepatitis (for hepatitis B: HBsAg positive and HBV DNA ≥ 500 IU/ml; for hepatitis C: HCV antibody positive and HCV viral load \> upper limit of normal);
• Psychiatric disorder that makes the patient unable to comply with treatment;
• Allergy to paclitaxel or any component of the study drugs;
• History or evidence of any disease, condition, treatment, or laboratory abnormality that could interfere with the study results or the patient's full participation, or any other condition that, in the investigator's opinion, makes the patient unsuitable for enrollment.