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

Becotatug Vedotin Combined With Pucotenlimab in First-Line Treatment-Failed Advanced Biliary Tract Carcinoma: A Phase II Exploratory Clinical Study

Biliary tract carcinoma (BTC), including cholangiocarcinoma and gallbladder cancer, is a highly aggressive digestive system malignancy with limited treatment options after failure of first-line standard chemotherapy.

This open-label, single-arm, Phase II exploratory study aims to evaluate the efficacy and safety of Becotatug Vedotin combined with Pucotenlimab in patients with EGFR-positive advanced BTC who have failed first-line therapy. Participants will receive the combination regimen until the occurrence of disease progression, unacceptable toxicity, withdrawal of informed consent, death, pregnancy, investigator's decision to discontinue treatment, or study termination, whichever occurs first.The primary endpoint is objective response rate (ORR) assessed per RECIST v1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety.

Inclusion Criteria:

1. Age ≥ 18 years, male or female.

2. 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.

3. EGFR expression positive by immunohistochemistry (IHC) (+, ++, or +++).

4. Failed at least one line of standard systemic therapy.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Life expectancy ≥ 3 months.

7. At least one measurable lesion per RECIST v1.1 on CT or MRI.

8. Child-Pugh class A or B (<7 points).

9. 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.

10. No serious complications such as active gastrointestinal bleeding, perforation, jaundice, gastrointestinal obstruction, or fever (>38°C) not attributable to cancer.

11. 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.

12. Expected to have good compliance with protocol-specified follow-up for efficacy and safety assessments.

13. Able to understand the study and willing to provide written informed consent.

Exclusion Criteria:

1. 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.
2. EGFR expression negative by IHC.
3. Known central nervous system (CNS) metastases or carcinomatous meningitis, unless clinically stable for ≥ 4 weeks after radiotherapy or surgery and asymptomatic.
4. Psychiatric or neurological disorders that compromise the ability to comply with study procedures.
5. Prior treatment with MMAE-containing antibody-drug conjugate (ADC) therapy.
6. Planned or previous organ or bone marrow transplantation.
7. Active or history of autoimmune disease requiring systemic immunosuppressive therapy.
8. Receipt of live vaccine within 30 days prior to first dose. Inactivated seasonal influenza vaccines are allowed.
9. Uncontrolled cardiac conditions or symptoms.
10. Active infection or fever (unless clearly attributable to tumor).
11. History or evidence of interstitial lung disease or active non-infectious pneumonitis.
12. 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.
13. Known hypersensitivity to any component of the study drugs.
14. Use of systemic immunosuppressive agents or corticosteroids (> 10 mg/day prednisone equivalent) within 14 days prior to enrollment.
15. Receipt of radiotherapy, chemotherapy, targeted therapy, or immunotherapy within 4 weeks prior to enrollment.
16. Participation in another interventional clinical trial within 4 weeks prior to enrollment.
17. Pregnancy or breastfeeding.
18. Any other condition that, in the investigator's judgment, makes the patient inappropriate for study participation.