M108 Plus CAPOX Versus Placebo Plus CAPOX as First-line Treatment for Claudin (CLDN) 18.2-Positive, HER2-Negative, PD-L1 CPS<5, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma.

The aim of this phase 3, double-blind, randomized, placebo-controlled study is to explore the efficacy and safety of M108 monoclonal antibody plus chemotherapy versus placebo plus chemotherapy as first-line treatment for Claudin (CLDN) 18.2-Positive, HER2-Negative, PD-L1 CPS<5, locally advanced or metastatic gastric/GEJ adenocarcinoma. Patients will be randomized in a 1:1 ration to receive M108 monoclonal antibody plus chemotherapy or placebo plus chemotherapy.

Inclusion criteria

• Written informed consent
• Histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma with no treatment previously. For patients with neoadjuvant/adjuant chemotherapy in the past, duration of last therapy to recurrence should be more than 6 months
• At least 1 measurable site of the disease according to RECIST 1.1 criteria.
• Positive CDLN 18.2 expression
• Negative HER2 expression, PD-L1 CPS<5
• ECOG performance status (PS) 0-1
• Life expectancy > 3 months
• Age ≥ 18 years and ≤75 years
• Adequate haematological/ coagulation/ hepatic/ renal function
• Men and women of childbearing age should agree to use effective contraception from the time they sign their informed consent until 3 months after the last dosing. Female subjects of childbearing age must have a negative blood beta-HCG test within 72 hours prior to first dosing.

Exclusion criteria

• Previous radiotherapy within 4 weeks prior to the start of study treatment. (if palliative radiotherapy was given to bone metastases and the patient recovered from acute toxicity was allowed).
• Previous anti-tumor therapy within 4 weeks prior to the start of study treatment.
• Previous major operation within 4 weeks prior to the start of study treatment.
• Have a prior severe allergic reaction or intolerance to known components of M108 monoclonal antibodies or other monoclonal antibodies (including humanized or chimeric antibodies); Allergic or intolerant to any component of capecitabine, oxaliplatin, etc.
• Subject who has been treated with CLDN18.2 monoclonal/bispecific antibodies, CLDN18.2 CAR-T, CLDN18.2 ADC and any therapies that target CLDN18.2.
• Subject who is in pregnant or in lactation period.
• Other clinically significant disease which may have adversely affected the safe delivery of treatment within this study.