Becotatugvedotin Plus Pucotenlimab in EGFR-Positive Advanced Gastric/GEJ Adenocarcinoma

Inclusion Criteria: 1. Voluntarily provide written informed consent and be willing and able to comply with all study procedures and follow-up requirements. 2. Age 18 to 75 years, regardless of sex. 3. Histologically or cytologically confirmed unresectable locally advanced, recurrent, or metastatic gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma. 4. EGFR-positive tumor confirmed by immunohistochemistry (IHC) performed on archival or newly obtained tumor tissue. EGFR positivity is defined as IHC 1+, 2+, 3+, or 4+, corresponding to membrane staining in ≥1% of tumor cells. 5. Disease progression, recurrence, or intolerance following one prior line of systemic therapy for advanced or metastatic disease, including a fluoropyrimidine- and platinum-based regimen with or without a PD-1 inhibitor, and considered eligible for second-line treatment. Patients who relapse within 6 months after completion of neoadjuvant or adjuvant chemotherapy are considered to have failed first-line therapy. 6. At least one measurable lesion according to RECIST version 1.1. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 8. Estimated life expectancy of at least 12 weeks. 9. Adequate organ function within 14 days prior to enrollment: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; Platelet count ≥100 × 10⁹/L; Hemoglobin ≥90 g/L; Total bilirubin ≤1.5 × upper limit of normal (ULN); AST and ALT ≤2.5 × ULN (≤5 × ULN in patients with liver metastases); Serum creatinine ≤1.5 × ULN or creatinine clearance (CrCl) ≥50 mL/min; INR ≤1.5 × ULN, or therapeutic anticoagulation with stable coagulation parameters considered acceptable by the investigator. 10. Women of childbearing potential must have a negative pregnancy test before enrollment. Male and female participants of reproductive potential must agree to use effective contraception during study treatment and for at least 6 months after the last dose of study drug. Exclusion Criteria: 1. Prior treatment with any EGFR-targeting antibody-drug conjugate (ADC), including becotatug vedotin (MRG003) or similar EGFR-targeting ADCs. Previous treatment with anti-EGFR monoclonal antibodies (e.g., cetuximab) is permitted. 2. Receipt of chemotherapy, targeted therapy, immunotherapy, or other anti-cancer therapy within 4 weeks before study treatment initiation, or unresolved treatment-related toxicities \> Grade 1 (except alopecia). Radiotherapy within 4 weeks (or palliative radiotherapy within 2 weeks) before enrollment. 3. HER2-positive disease (IHC 3+ or IHC 2+ with ISH/FISH amplification). 4. Untreated or uncontrolled central nervous system (CNS) metastases or leptomeningeal disease. Patients with previously treated brain metastases may be enrolled if clinically stable for at least 4 weeks and receiving no more than prednisone 10 mg/day (or equivalent). 5. Current or previous interstitial lung disease (ILD), immune-related pneumonitis, or active pneumonitis requiring systemic corticosteroid treatment. 6. Active autoimmune disease requiring systemic immunosuppressive therapy, or history of organ transplantation requiring immunosuppressive treatment. 7. Uncontrolled active infection, including severe bacterial infection requiring intravenous antibiotics, active tuberculosis, hepatitis B virus (HBV) DNA \>2,000 IU/mL or without appropriate antiviral therapy, untreated hepatitis C virus (HCV) infection with detectable HCV RNA, or uncontrolled human immunodeficiency virus (HIV) infection. 8. Significant cardiovascular or other serious uncontrolled systemic diseases, including myocardial infarction, unstable angina, New York Heart Association (NYHA) class III-IV heart failure, severe arrhythmia, QTc \>470 ms within 6 months before enrollment, or any other condition judged by the investigator to interfere with study participation. 9. Baseline Grade ≥2 peripheral neuropathy or clinically significant sensory neuropathy. 10. Active gastrointestinal bleeding, gastrointestinal perforation, bowel obstruction, or gastrointestinal conditions requiring urgent surgical or interventional treatment. 11. History of another active malignancy within the previous 5 years, except adequately treated basal cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies with negligible risk of recurrence. 12. Pregnant or breastfeeding women, or individuals planning pregnancy during the study period. 13. Known severe hypersensitivity to becotatug vedotin, pucotenlimab, or any of their excipients. 14. Any medical, psychiatric, social, or compliance-related condition that, in the opinion of the investigator, would compromise participant safety, interfere with study participation, or affect interpretation of study results. 15. Participation in another interventional clinical trial within 4 weeks before enrollment or concurrent participation in another clinical trial involving investigational agents.