Zolbetuximab, Durvalumab, and FLOT Combination Neoadjuvant Chemotherapy for CLDN18.2-Positive Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Prior treatment

• Patients who have used another investigational drug or device within 28 days before the first dose of study drug.
• Patients with a history of systemic immunosuppressive therapy, such as systemic corticosteroids, within 14 days before the first dose of study drug.
• Patients who have experienced unstable angina, myocardial infarction, or intervention/hospitalization for heart failure due to ventricular arrhythmia within 6 months before the first dose of study drug.
• Patients with active infection requiring systemic treatment who have not fully recovered within 7 days before the first dose of study drug.
• Patients with active autoimmune disease requiring systemic immunosuppressive therapy within 3 months before the first dose of study drug.
• Patients who have undergone major surgery within 28 days before the first dose of study drug.
• Patients who have not fully recovered from major surgery by 14 days before the first dose of study drug.
• Patients who are ineligible for FLOT therapy or durvalumab administration due to a history of prior conditions or comorbidities.

Other illness

• Patients with a history of severe allergic reaction or intolerance to zolbetuximab or to known components of humanized or chimeric monoclonal antibodies.
• Patients known to have immediate or delayed hypersensitivity to any component of the study drugs, or for whom any component of the study drugs is contraindicated.
• Patients with significant gastric bleeding and/or untreated gastric ulcer judged by the investigator to be inappropriate for participation in this study.
• Patients with central nervous system metastasis and/or carcinomatous meningitis from gastric/GEJ cancer.
• Patients known to be positive for human immunodeficiency virus infection, or known to have active hepatitis B (positive for hepatitis B surface antigen) or hepatitis C infection.
• Patients with a clinically significant disease or comorbidity that, in the investigator's judgment, would adversely affect the safe conduct of treatment in this study or make the patient inappropriate for participation.
• Patients with a psychiatric disorder or social situation that, in the investigator's judgment, could interfere with compliance with the study.
• Patients judged by the investigator to have another malignancy requiring treatment.
• Patients meeting any of the following (surgical-related):
  • (ア) Judged by the investigator to be unresectable with curative intent. (イ) Meets the following criterion for local disease by clinical TNM staging: cT1N0.

Other

• Patients with complete gastric outlet obstruction, or partial obstruction with persistent recurrent vomiting.

• Histologically confirmed gastric cancer (either a general histological type or a lymphoid stroma-type carcinoma) on endoscopic biopsy from the primary lesion in the stomach or gastroesophageal junction.
• No prior chemotherapy, radiotherapy, or immunotherapy, including treatment for other cancers, and classified as cT2-4 and/or cN+ M0 according to the UICC TNM Classification, 8th edition.
• Moderate or greater membranous staining in \>-75% of tumor cells confirmed by CLDN18.2 immunohistochemistry.
• No distant metastasis on contrast-enhanced CT of the chest, upper abdomen, and pelvis.
• No prior treatment with an immune checkpoint inhibitor.
• Age \>=18 years at the time of enrollment.
• ECOG Performance Status (PS) of 0 or 1.
• No history of any surgical treatment for gastric cancer other than endoscopic resection (ESD or EMR).
• No marked bleeding or severe stenosis from the gastric cancer lesion.
• Laboratory test values obtained within 14 days before enrollment meet a given criteria.
• Written consent to participate in the study has been obtained from the patient.
• Female patients are not pregnant and meet all of the following:
  • Not a woman of childbearing potential (WOCBP), or agrees to follow the contraception guidance throughout the treatment period, for at least 9 months after the last dose of oxaliplatin, and for at least 6 months after the last dose of all other study drugs.
  • Agrees not to breastfeed during the screening period, the study period, and for 6 months after the last dose of study drug.
  • Agrees not to donate ova during the screening period, the study period, for 9 months after the last dose of oxaliplatin, and for 6 months after the last dose of all other study drugs.
  • Male patients with a female partner of childbearing potential agree to use contraception during the study period and for at least 6 months after the last dose of study drug. Male patients with a pregnant or breastfeeding partner agree to remain abstinent or use a condom during that period. Male patients agree not to donate sperm from the start of screening through 6 months after the last dose of study drug.