Enfortumab Vedotin in Patients With Advanced Small Bowel Adenocarcinoma Refractory or Intolerant to Platinum-based Combination Therapy

Inclusion Criteria: 1. Histologically or cytologically confirmed small bowel adenocarcinoma (duodenum excluding the ampulla of Vater, jejunum, or ileum). If pathology was performed at another institution, slides/blocks must be reviewed by a pathologist at the study site before enrollment. 2. One of the following: 1. unresectable locally advanced small bowel adenocarcinoma in which R0 resection would require combined resection of invaded organs and is judged infeasible 2. UICC-TNM stage IV small bowel adenocarcinoma with distant metastasis 3. postoperative recurrence of small bowel adenocarcinoma. 3. No symptomatic brain metastases, carcinomatous meningitis, or spinal metastases requiring radiation or surgical intervention. 4. No clinically significant pericardial effusion, pleural effusion, or ascites requiring treatment. 5. Age ≥18 years at registration. 6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1. 7. ≥1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, on contrast-enhanced CT (slice thickness ≤5 mm) obtained within 14 days before registration. 8. Prior platinum-based chemotherapy for unresectable locally advanced or metastatic small bowel adenocarcinoma (FOLFOX or CapeOX) with documented progression, recurrence or treatment discontinuation due to toxicity. 9. If prior testing (e.g., microsatellite instability, mismatch repair, or comprehensive genomic profiling) has identified alterations that qualify for tumor-agnostic approved therapies, the patient must be refractory, intolerant, or ineligible to such therapies. These tests are not mandatory; lack of testing does not preclude enrollment. 10. Archival tumor tissue is available; if unavailable, the patient agrees to a pre-treatment biopsy to obtain tumor tissue. 11. No anticancer chemotherapy or radiotherapy within 14 days before registration. 12. No surgery under general anesthesia within 28 days before registration. 13. Screening laboratory tests within 14 days before registration meet all of the following conditions: 1. absolute neutrophil count ≥1,500/mm³ 2. platelet count≥100,000/mm³ 3. hemoglobin ≥8.5 g/dL 4. AST ≤100 U/L (≤200 U/L with liver metastases) 5. ALT ≤100 U/L (≤200 U/L with liver metastases) 6. total bilirubin ≤1.5 mg/dL 7. serum creatinine ≤1.5 mg/dL 14. Contraception: Women of childbearing potential agree to use effective contraception and to refrain from oocyte donation from consent through ≥2 months after last dose; breastfeeding patients agree to withhold breastfeeding for ≥3 weeks after last dose; men agree to use effective contraception and to refrain from sperm donation from consent until ≥1 month after last dose. 15. Written informed consent obtained from the patient. Exclusion Criteria: 1. Active second primary malignancy. 2. Active infection requiring systemic therapy. 3. Interstitial lung disease/pneumonitis, diagnosed by imaging or clinical findings, current or prior, irrespective of steroid use. 4. Poorly controlled diabetes mellitus: HbA1c ≥8%, or HbA1c 7.0-\<8.0% with otherwise unexplained hyperglycemic symptoms (polyuria and/or polydipsia). 5. Known hypersensitivity to enfortumab vedotin, its excipients (e.g., histidine, trehalose dihydrate, polysorbate 20). 6. Ongoing grade ≥2 sensory or motor peripheral neuropathy. 7. Cerebrovascular event, unstable angina, myocardial infarction, or severe heart failure within 6 months before registration. 8. Ongoing grade ≥2 unresolved clinically significant toxicities from prior therapy, excluding alopecia. 9. Ongoing grade ≥2 dermatologic disorders regardless of prior-treatment causality. 10. Ongoing use of chronic systemic corticosteroids or other immunosuppressants. 11. Active keratitis or corneal ulcer. 12. Positive for HIV antibodies, HBs antigen, or HCV RNA 13. Negative for HBs antigen, positive for HBs or HBc antibodies, and positive HBV DNA quantification (patients are not excluded if HBV DNA is detected but below the limit of quantification). 14. Pregnant or possibly pregnant women. 15. Psychiatric illness or psychiatric symptoms that interfere with activities of daily living and, in the investigator's judgment, preclude study participation.