Single-arm, Multicenter, Open-label Phase II Study of Vedotin for Injection in Second-line or Later Treatment of Advanced Biliary Tract Cancer

• MRG003 (Becotatug Vedotin) (Biological): Becotatug vedotin 2.3 mg/kg, intravenous infusion over 60 minutes (±15 min), Q3W (every 21 days).

Primary outcomes

• Objective Response Rate [From first study drug administration until documented disease progression or death, up to approximately 24 months.]: ORR assessed by investigator according to RECIST version 1.1 (CR + PR).

Secondary outcomes

• Progression-Free Survival (PFS) [Up to approximately 24 months.]: Time from first dose to first documented disease progression (RECIST 1.1) or death from any cause.
• Disease Control Rate (DCR) [From first dose until disease progression, up to approximately 24 months.]: Percentage of participants with CR, PR or SD per RECIST 1.1.
• Time from first dose to death from any cause. [Up to approximately 30 months.]: Time from first dose to death from any cause.
• Safety-Incidence of Adverse Events (AEs) and Serious Adverse Events [From signing informed consent through 30 days after last study drug dose.]: Incidence, severity (NCI-CTCAE v5.0) of AEs/SAEs, laboratory abnormalities, vital-sign changes.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Aged 18-80 years, of any gender.
2. Patients with histologically or cytologically confirmed primary advanced biliary tract carcinoma (BTC), including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gallbladder carcinoma (GBC), and recurrent biliary tract carcinoma.
3. EGFR IHC-positive assessed by a pathological laboratory.
4. Have received at least one line of prior systemic therapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Expected survival ≥ 3 months.
7. At least one measurable target lesion assessable by CT or MRI according to RECIST version 1.1.
8. Laboratory test results meeting the following criteria:

(1) Hematologic function: Hemoglobin (Hb) ≥90 g/L; white blood cell count (WBC) ≥ lower limit of normal (LLN); absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count ≥100×10⁹/L.

(2) Renal function: Creatinine ≤1.5 × upper limit of normal (ULN); creatinine clearance (Ccr) ≥55 mL/min.

(3) Hepatic function: Total bilirubin ≤1.5 × ULN; ALT and AST ≤2.5 × ULN. (For patients with intrahepatic cholangiocarcinoma or liver metastases: total bilirubin ≤3 × ULN; ALT and AST ≤5 × ULN).

9\. Absence of severe complications, such as active gastrointestinal hemorrhage, perforation, jaundice, gastrointestinal obstruction, or non-neoplastic fever >38 °C.

10\. Women of child-bearing potential: agree to use contraception during the study and for 6 months after the last study treatment; have a negative serum or urine pregnancy test within 7 days prior to enrollment; and are not lactating. Male patients: agree to use contraception during the study and for 6 months after the last study treatment.

11\. Expected good compliance and ability to follow study procedures for efficacy and safety follow-up.

12\. Able to understand the study and provide written informed consent voluntarily.

Exclusion Criteria:

1. Diagnosis of other malignant tumors within the past 5 years, except for carcinoma in situ and basal cell carcinoma.
2. Known central nervous system metastases (excluding patients with stable, asymptomatic disease 4 weeks after radiotherapy or surgery), or evidence of carcinomatous meningitis.
3. Psychiatric or neurological disorders that may impair subject compliance with study requirements.
4. Prior treatment with MMAE-payload antibody-drug conjugates (ADCs).
5. Planned or prior organ or bone marrow transplantation.
6. Administration of live vaccines within 30 days before the first study drug dose. Inactivated seasonal injectable influenza vaccine is permitted.
7. Uncontrolled clinically significant cardiac signs or diseases.
8. Active infection or fever (excluding documented tumor-related fever).
9. History or evidence of interstitial lung disease or active non-infectious pneumonitis.
10. Other medical conditions rendering the subject ineligible for enrollment, including immunodeficiency, active pulmonary tuberculosis, positive hepatitis C virus test, uncorrectable electrolyte disturbances, uncontrolled pericardial, pleural or peritoneal effusion. Patients with hepatitis B may be enrolled if HBV-DNA < 500 IU/mL and liver function is normal after treatment.
11. Known hypersensitivity to any study drug or its excipients.
12. Receipt of radiotherapy, chemotherapy, targeted therapy or immunotherapy within 4 weeks prior to enrollment.
13. Participation in another interventional drug clinical trial within 4 weeks prior to enrollment.
14. Pregnant or lactating women.
15. Subjects deemed inappropriate for enrollment at the investigator's discretion.