Overview

This trial is a registrational Phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-M05D1 in patients with Claudin (CLDN) 18.2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC) who have received prior first-line treatment.

Eligibility

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. No gender restrictions;
3. Age: ≥18 years and ≤75 years;
4. Expected survival time ≥3 months;
5. Pathologically confirmed locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma;
6. Patients who have failed prior first-line standard therapy must have evidence of radiographic clear progression;
7. Ability to provide archived or fresh tumor tissue;
8. Must have at least one measurable lesion as defined by RECIST v1.1;
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
10. Toxicity from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
11. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
12. Organ function levels must meet the requirements;
13. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × upper limit of normal (ULN);
14. Urine protein ≤2+ or \<1000 mg/24h;
15. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, with serum pregnancy test negative, and must be non-lactating; all enrolled patients (regardless of male or female) must take adequate barrier contraceptive measures throughout the entire treatment period and for 6 months after treatment completion.

Exclusion Criteria:

1. Prior anti-tumor treatment;
2. Positive HER2 expression in tumor tissue;
3. History of severe cardiovascular or cerebrovascular disease;
4. Prolonged QT interval, complete left bundle branch block, third-degree atrioventricular block, frequent and uncontrollable arrhythmias;
5. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to screening;
6. Active autoimmune diseases and inflammatory diseases;
7. Diagnosis of another malignancy within 3 years prior to the first dose;
8. Hypertension poorly controlled by two antihypertensive medications;
9. History of interstitial lung disease (ILD) requiring hormone therapy, etc.;
10. Concurrent pulmonary disease resulting in clinically severe respiratory impairment;
11. Infection requiring clinical intervention within 2 weeks prior to randomization;
12. Patients with poorly controlled blood glucose levels;
13. Patients with active central nervous system metastases;
14. Patients with large serous cavity effusions, symptomatic serous cavity effusions, or poorly controlled serous cavity effusions;
15. Imaging findings indicating tumor invasion or encasement of major blood vessels such as those in the chest, neck, or pharynx;
16. History of allergic reactions to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient of BL-M05D1;
17. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
18. Positive for human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
19. Active infection requiring systemic treatment;
20. Pregnant or breastfeeding women;
21. Esophageal or gastric varices requiring intervention within the past three months, etc.;
22. History of intestinal obstruction, inflammatory bowel disease, or extensive bowel resection, etc.;
23. Presence of other serious physical or laboratory abnormalities, or poor compliance, which may increase the risk of participating in the study, interfere with study results, or make the patient unsuitable for participation in the study as judged by the investigator.