Becotatug Vedotin Plus Pucotenlimab for Advanced Biliary Tract Cancer, Phase II

Inclusion criteria

• Age ≥ 18 years, male or female.
• Histologically or cytologically confirmed advanced biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC); recurrent biliary tract cancer is also eligible.
• EGFR expression positive by immunohistochemistry (IHC) (+, ++, or +++).
• Failed at least one line of standard systemic therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 3 months.
• At least one measurable lesion per RECIST v1.1 on CT or MRI.
• Child-Pugh class A or B (<7 points).
• Adequate organ function as defined below:

• Hematologic: 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.
• Renal: Serum creatinine ≤ 1.5 × upper limit of normal (ULN); creatinine clearance (CrCl) ≥ 55 mL/min.
• Hepatic: Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN (or ≤ 3 × ULN for total bilirubin and ≤ 5 × ULN for ALT/AST in patients with intrahepatic cholangiocarcinoma or liver metastases).
• Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN; partial thromboplastin time (PTT) within normal range.
• No serious complications such as active gastrointestinal bleeding, perforation, jaundice, gastrointestinal obstruction, or fever (>38°C) not attributable to cancer.
• Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment, must not be breastfeeding, and must agree to use effective contraception during the study and for 6 months after the last dose. Male participants must agree to use effective contraception during the study and for 6 months after the last dose.
• Expected to have good compliance with protocol-specified follow-up for efficacy and safety assessments.
• Able to understand the study and willing to provide written informed consent.

Exclusion criteria

• Diagnosis of another primary malignancy within 5 years prior to enrollment, except for adequately treated carcinoma in situ or basal cell carcinoma of the skin.
• EGFR expression negative by IHC.
• Known central nervous system (CNS) metastases or carcinomatous meningitis, unless clinically stable for ≥ 4 weeks after radiotherapy or surgery and asymptomatic.
• Psychiatric or neurological disorders that compromise the ability to comply with study procedures.
• Prior treatment with MMAE-containing antibody-drug conjugate (ADC) therapy.
• Planned or previous organ or bone marrow transplantation.
• Active or history of autoimmune disease requiring systemic immunosuppressive therapy.
• Receipt of live vaccine within 30 days prior to first dose. Inactivated seasonal influenza vaccines are allowed.
• Uncontrolled cardiac conditions or symptoms.
• Active infection or fever (unless clearly attributable to tumor).
• History or evidence of interstitial lung disease or active non-infectious pneumonitis.
• Any other condition that makes the patient unsuitable for enrollment, including but not limited to: immunodeficiency; active tuberculosis; hepatitis B (eligible if HBV-DNA < 500 IU/mL with normal liver function after antiviral therapy); hepatitis C virus (HCV) infection; uncorrectable electrolyte disturbances; uncontrolled pericardial effusion, pleural effusion, or ascites.
• Known hypersensitivity to any component of the study drugs.
• Use of systemic immunosuppressive agents or corticosteroids (> 10 mg/day prednisone equivalent) within 14 days prior to enrollment.
• Receipt of radiotherapy, chemotherapy, targeted therapy, or immunotherapy within 4 weeks prior to enrollment.
• Participation in another interventional clinical trial within 4 weeks prior to enrollment.
• Pregnancy or breastfeeding.
• Any other condition that, in the investigator's judgment, makes the patient inappropriate for study participation.