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.

Study Overview

• Status: Not yet recruiting
• Conditions: Biliary Tract Cancer (BTC); EGFR-positive Advanced Biliary Tract Carcinoma
• Intervention / Treatment: Drug: Becotatug Vedotin; Drug: Pucotenlimab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Huikai Li, MD; Phone Number: 86+18622228639; Email: vianvianvip@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Becotatug Vedotin + Pucotenlimab; The combination regimen will be continued 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.	Drug: Becotatug Vedotin; 2.0mg/kg ，IV，D1，Q3W；The infusion duration is 60 minutes ± 15 minutes, with the first infusion lasting no less than 60 minutes.; Other Names: MRG003; Drug: Pucotenlimab; 200mg，IV，D1，Q3W；The infusion duration is 60 minutes ± 15 minutes, with the first infusion lasting no less than 60 minutes.; Other Names: HX008

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate is defined as the proportion of patients achieving complete response (CR) or partial response (PR) assessed per RECIST v1.1.	From start of treatment until disease progression, assessed up to 36 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Time from the first dose of study treatment to the first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first.	From start of treatment to disease progression or death, assessed up to 36 months.
Overall Survival (OS)	Time from the first dose of study treatment to death from any cause.	From start of treatment to death, assessed up to 36 months.
Disease Control Rate (DCR)	Proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1.	From start of treatment until disease progression, assessed up to 36 months.
Duration of Response (DOR)	Time from the first documented objective response (CR or PR) to the first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first.	From first response to disease progression or death, assessed up to 24 months from response.
Safety and Tolerability	Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs) assessed by NCI CTCAE v5.0.	From first dose of study drug until 30 days after last dose, up to 36 months

Collaborators and Investigators

• Sponsor: HuiKai Li

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 10, 2026
• First Submitted That Met QC Criteria: June 10, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: PD-1; Second-line; Pucotenlimab; Becotatug Vedotin; EGFR-ADC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Biliary Tract Neoplasms
• Other Study ID Numbers: EC-2026-0002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No