Inclusion Criteria:
1. Voluntary participation in the study and provision of written informed consent.
2. Male or nonpregnant female patients aged 18-70 years.
3. Life expectancy of at least 3 months.
4. Histologically or cytologically confirmed recurrent or metastatic nasopharyngeal carcinoma (NPC) with treatment failure following prior platinum-based chemotherapy or PD-(L)1 inhibitor therapy. The two treatment modalities may have been administered concurrently as part of a first-line regimen or sequentially. Patients must be considered unsuitable for curative local salvage treatment, including surgery, re-irradiation, or other definitive local therapies.
5. At least one measurable lesion according to RECIST version 1.1. Previously irradiated lesions cannot be selected as target lesions unless unequivocal progression has been documented at least 3 months after the last radiotherapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Adequate hematologic function, defined as:
* Hemoglobin ≥90 g/L;
* White blood cell count ≥4.0 × 10⁹/L;
* Platelet count ≥100 × 10⁹/L.
8. Adequate hepatic function, defined as:
* Total bilirubin \<2.0 × upper limit of normal (ULN);
* AST and ALT ≤2.5 × ULN in patients without liver metastases, or ≤3.0 × ULN in patients with liver metastases;
* Alkaline phosphatase ≤1.5 × ULN, or ≤2.0 × ULN in patients with liver metastases;
* Serum albumin ≥30 g/L.
9. Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT), and activated partial thromboplastin time (APTT) ≤1.5 × ULN. Patients receiving anticoagulant therapy are eligible if their anticoagulation parameters are within the therapeutic range and are closely monitored by the investigator.
10. Adequate renal function, defined as serum creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min calculated using the adjusted Cockcroft-Gault formula if serum creatinine exceeds 1.5 × ULN.
11. Women of childbearing potential and male patients of reproductive potential must agree to use adequate contraception throughout study treatment and for 180 days after the last dose of study treatment.
Exclusion Criteria:
1. Histologically confirmed keratinizing squamous cell carcinoma (WHO type I).
2. Grade ≥2 peripheral neuropathy according to CTCAE version 5.0.
3. Anticipated requirement for surgery or any other systemic or local anticancer therapy during the study, including palliative treatment, except for palliative treatment directed at non-target lesions.
4. Receipt of any of the following treatments before the first dose of study treatment:
* Systemic chemotherapy within 3 weeks;
* Small-molecule targeted therapy within 2 weeks or 5 half-lives, whichever is longer;
* Anticancer biological therapy, macromolecular targeted therapy, or immunotherapy within 4 weeks;
* Major surgery within 4 weeks, except for minor surgery performed within 2 weeks with complete recovery;
* Radiotherapy within 14 days, or radiotherapy to the central nervous system within 28 days.
5. Known active central nervous system (CNS) metastases or carcinomatous meningitis. Patients with previously treated brain metastases may be eligible if clinically stable, without progressive or new neurological deficits, seizures, evidence of increased intracranial pressure, vomiting, or headache, and without evidence of lesion enlargement on MRI during the preceding 4 weeks or a requirement for corticosteroids during the 14 days before the first dose of study treatment.
6. Residual toxicities from previous anticancer treatment, including immunotherapy, targeted therapy, chemotherapy, or radiotherapy, or clinically significant laboratory abnormalities greater than grade 1 according to CTCAE version 5.0, except for alopecia, fatigue, and grade 2 hypothyroidism.
7. Uncontrolled or poorly controlled cardiovascular disease, including any of the following:
* Grade ≥2 congestive heart failure within 6 months before enrollment;
* Myocardial infarction or unstable angina;
* History of ventricular tachycardia or torsades de pointes;
* Clinically significant arrhythmias requiring treatment;
* QTcF \>450 ms in males or \>470 ms in females;
* Complete left bundle branch block or third-degree atrioventricular block.
8. Pulmonary embolism or deep vein thrombosis within 3 months before the first dose of study treatment, except for thrombosis associated with an implanted venous port or peripherally inserted central catheter (PICC).
9. History of another malignancy unless the patient has received potentially curative treatment and remained recurrence-free for at least 5 years. Exceptions include adequately treated basal cell carcinoma of the skin, superficial bladder cancer, cutaneous squamous cell carcinoma, carcinoma in situ, and papillary thyroid carcinoma.
10. Any severe or uncontrolled systemic disease, including poorly controlled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg) or poorly controlled diabetes mellitus (HbA1c \>8%).
11. Active bleeding, history of a bleeding or coagulation disorder, or current treatment with coumarin anticoagulants.
12. Known hypersensitivity to any component or excipient of becotatug vedotin, including citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, sodium chloride, and polysorbate 80; or a history of grade ≥3 hypersensitivity reactions to other anti-EGFR agents or monoclonal antibodies.
13. Active hepatitis B or hepatitis C infection, defined as:
* Hepatitis B surface antigen (HBsAg) positivity with HBV DNA ≥500 IU/mL;
* Hepatitis C antibody positivity with detectable HCV RNA above the lower limit of detection.
Patients with other severe liver diseases, including chronic autoimmune liver disease, primary biliary cirrhosis, sclerosing cholangitis, alcoholic liver disease, or nonalcoholic steatohepatitis (NASH), will also be excluded.
14. Severe uncontrolled infection, known HIV infection, or acquired immunodeficiency syndrome (AIDS); active autoimmune disease, except for type 1 diabetes mellitus, hypothyroidism controlled with replacement therapy, or skin disorders not requiring systemic treatment (such as vitiligo, psoriasis, or alopecia); or a history of allogeneic tissue or organ transplantation, stem cell transplantation, or bone marrow transplantation.
15. Active bacterial, viral, fungal, rickettsial, or parasitic infection requiring systemic antimicrobial treatment, unless adequately treated and resolved before the first dose of study treatment.
16. Receipt of a live-virus vaccine within 30 days before the first dose of study treatment.
17. History of or concurrent interstitial pneumonitis, severe chronic obstructive pulmonary disease with respiratory failure, severe pulmonary dysfunction, or symptomatic bronchospasm.
18. Receipt of immunologically based treatment for any reason, including chronic systemic corticosteroid therapy equivalent to \>10 mg/day of prednisone within 7 days before the first dose of study treatment or during study participation. Inhaled or topical corticosteroids, systemic corticosteroids equivalent to ≤10 mg/day of prednisone, and short-term corticosteroid use at higher doses for specific indications (such as premedication before contrast administration) are permitted.
19. Uncontrolled pleural, abdominal, pelvic, or pericardial effusion requiring drainage at least once per month.
20. Positive pregnancy test, current breastfeeding, or unwillingness to use adequate contraception during study treatment and for 180 days after the last dose of study treatment.
21. Any other disease, clinically significant laboratory abnormality, serious medical or psychiatric condition, or substance abuse (including alcohol abuse) that, in the investigator's judgment, may compromise patient safety, study integrity, study participation, or interpretation of study results.
