LM-302 plus oral S-1 and intraperitoneal paclitaxel, with or without cadonilimab, for Claudin 18.2–positive advanced stomach or GEJ cancer with peritoneal spread

LM-302 and S-1 Plus Intraperitoneal Paclitaxel With or Without Cadonilimab for Claudin 18.2-positive Gastric Cancer With Peritoneal Metastasis: a Prospective, Exploratory Study

This trial tests whether adding cadonilimab to LM-302, oral S-1, and intraperitoneal paclitaxel helps people with Claudin 18.2–positive gastric or gastroesophageal junction cancer that has spread to the peritoneum.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: Cadonilimab
• Locations: 1 site (Shanghai, Huangpu District)
• Trial ID: NCT07556640 on ClinicalTrials.gov

What this trial studies

This is a prospective, exploratory phase 2 interventional trial enrolling adults with HER2-negative, Claudin 18.2–positive gastric or gastroesophageal junction adenocarcinoma and confirmed peritoneal metastases. Participants receive LM-302 combined with oral S-1 and intraperitoneal paclitaxel, and some participants also receive cadonilimab. Key eligibility includes Claudin 18.2 expression ≥25% (moderate to strong), ECOG performance status ≤1, and adequate organ function, with peritoneal disease confirmed by laparoscopy. The study will monitor safety, tolerability, and preliminary anti-tumor activity in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with histologically confirmed HER2-negative gastric or GEJ adenocarcinoma, laparoscopically confirmed peritoneal metastases, Claudin 18.2 expression ≥25%, ECOG ≤1, expected life expectancy >3 months, and adequate organ function.

Not a fit: Patients with distant metastases beyond the peritoneum, prior Claudin 18.2–targeted therapy, poor performance status, pregnancy or breastfeeding, or uncontrolled CNS/mental disease are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the regimen could improve control of peritoneal disease and potentially extend survival or relieve symptoms for patients with Claudin 18.2–positive gastric/GEJ cancer.

How similar studies have performed: Other Claudin 18.2–targeted therapies have shown promising activity in advanced gastric cancer, but combining LM-302 with intraperitoneal paclitaxel and cadonilimab is exploratory and not yet proven.

Eligibility criteria

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.

Where this trial is running

Shanghai, Huangpu District

• Ruijin Hospital Shanghai Jiao Tong University School of Medicine — Shanghai, Huangpu District, China (Recruiting)

Study contacts

• Study coordinator: Zhongyin Yang

Conditions Gastric Cancer Stage IV; Peritoneal Metastases From Gastric Cancer; Gastric or Esophagogastric Junction Adenocarcinoma; Gastric cancer; Peritoneal metastasis; Claudin 18.2; Cadonilimab; Paclitaxel