A Study of FG-M108+Chemotherapy vs Placebo+Chemotherapy in Claudin18.2-positive Pancreatic Cancer

This is a multicenter, randomized, double-blind, placebo-controlled phase 3 study designed to evaluate the efficacy and safety of FG-M108 injection combined with Nab-P+GEM versus placebo combined with Nab-P+GEM as first-line treatment in patients with Claudin18.2-positive, unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma.

Inclusion criteria

• Voluntarily sign the informed consent form, understand the study, are willing to comply with and have the ability to complete all trial procedures;
• Age 18-80 years (inclusive), any gender;
• Histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma, without prior systemic therapy; or for subjects who have received prior neoadjuvant/adjuvant chemotherapy, the time from the last treatment to disease recurrence is >6 months;
• Able to provide archived or fresh pathological tissue for CLDN18.2 testing, with central laboratory testing confirming tumor tissue CLDN18.2 positive (defined as ≥40% of tumor cells with CLDN18.2 membrane staining ≥2+ by central laboratory IHC);
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• Have at least one measurable tumor lesion according to RECIST 1.1 criteria;
• Expected survival ≥3 months;
• Adequate cardiac, bone marrow, liver, renal function;

Exclusion criteria

• Have received a live vaccine within 4 weeks prior to randomization;
• Have received radiotherapy within 2 weeks prior to randomization;
• Have received other anti-tumor drug therapy within 4 weeks or within 5 half-lives of the anti-tumor drug prior to randomization;
• Have undergone major surgery within 4 weeks prior to randomization;
• Have received any clinical study drug treatment within 4 weeks prior to randomization;
• Have previously received any treatment targeting CLDN18.2, such as CLDN18.2 monoclonal/bispecific antibodies, CLDN18.2 CAR-T, or CLDN18.2 ADC;
• Have a history of other (non-study tumor) malignancies within 3 years prior to randomization;
• Have a history of central nervous system metastases and/or carcinomatous meningitis;
• Have adverse reactions from prior treatments that have not recovered to CTCAE v5.0 Grade ≤1 (excluding alopecia and anemia) prior to randomization;
• Have had clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to randomization;
• Have uncontrolled systemic diseases assessed by the investigator, including diabetes, hypertension, pulmonary fibrosis, interstitial lung disease, etc.;
• The investigator judges the subject to have obvious active gastrointestinal bleeding;
• Known history of Hepatitis C or chronic active Hepatitis B;
• Require systemic treatment with corticosteroids (dose >10 mg/day prednisone or equivalent dose of similar drugs) or other immunosuppressants within ≤14 days prior to randomization;
• Any other condition of the subject (e.g., psychological, geographical, or medical condition) that does not permit compliance with the study and follow-up procedures;
• Are pregnant or breastfeeding;