Vebotolimab Combined With Ptorlimab for EGFR-positive Refractory Advanced Biliary Tract Malignancies

An Exploratory Study of Vedotin-tislelizumab Combined With Toripalimab in EGFR-positive Refractory Advanced Biliary Tract Malignancies

This study aims to observe the efficacy and safety of the combination of vebecotototo monoclonal antibody and putli monoclonal antibody in the treatment of EGFR-positive refractory biliary malignant tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer of Biliary Duct
• Intervention / Treatment: Drug: Vibecotecotamab combined with Putilimab for EGFR-positive refractory biliary malignant tumors

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dan Cao; Phone Number: 86-28-85422589; Email: caodan@scu.edu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
      • Contact: Dan Cao; Phone Number: 86-28-85422589; Email: caodan@scu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Age 18 - 70 years old, gender not restricted;
2. Patients with untreated primary advanced biliary system malignancies diagnosed by pathological histology or cytology;
3. Physical condition: ECOG PS score 0 - 1;
4. Pathological laboratory assessment: EGFR IHC ≥ 1+;
5. Have undergone at least one line of systemic drug treatment;
6. According to the RECIST 1.1 standard, at least one measurable target lesion that can be detected by CT or MRI;

7. Laboratory test indicators meet the following requirements:

   ① Bone marrow function: Hemoglobin (Hb) ≥ 90g/L; White blood cell count (WBC) ≥ lower limit of normal value; Absolute neutrophil count (ANC) ≥ 1.5×10^9/L; Platelet count ≥ 100×10^9/L;

   ② Renal function: Cr ≤ UNL (upper limit of normal) × 1.5, endogenous creatinine clearance rate (Ccr) ≥ 55 ml/min;

   ③ Liver function: Total bilirubin ≤ ULN × 1.5; ALT and AST ≤ ULN × 2.5; (if it is intrahepatic cholangiocarcinoma or there is liver metastasis, total bilirubin not higher than 3 times the upper limit of normal, transaminase not higher than 5 times the upper limit of normal);

   ④ Coagulation function: International normalized ratio of prothrombin time ≤ ULN × 1.5, and partial thromboplastin time within the normal range;

8. Pregnant women agree to use contraception during the study period and within 6 months after the study ends; The serum or urine pregnancy test is negative within 7 days before the study entry, and non-lactating patients; Male patients agree to use contraception during the study period and within 6 months after the study ends;
9. Within 4 weeks before entry, have not participated in other drug clinical trials;
10. The subject can understand the situation of this study and voluntarily sign the informed consent form.
11. No severe complications such as active gastrointestinal bleeding, perforation, jaundice, gastrointestinal obstruction, non-cancerous fever > 38℃;
12. Expected good compliance, able to follow the protocol requirements for efficacy and adverse reactions follow-up.
13. Expected survival period > 3 months.

Exclusion criteria:

(1) Previously diagnosed with other malignant tumors within 5 years (excluding carcinoma in situ, basal cell carcinoma, etc.); (2) Known central nervous system metastasis (except for those with stable disease after radiotherapy or surgery for 4 weeks and no symptoms) or evidence of cancer meningitis; (3) Have mental or neurological disorders and cannot cooperate; (4) Patients who have received drugs with a loading dose of MMAE ADC drugs previously; (5) Patients preparing for or having previously received organ or bone marrow transplantation; (6) Have any active autoimmune diseases or autoimmune disease history; (7) Received live vaccines within 30 days before the first administration (allowing the use of injectable seasonal influenza vaccine as it is a killed vaccine); (8) Have uncontrolled clinical symptoms or diseases of interstitial lung disease or active non-infectious pneumonia history or evidence; (9) Have interstitial lung disease or active non-infectious pneumonia history or evidence within 4 weeks before entry; (10) Have other diseases that are not suitable for entry, such as immunodeficiency, active pulmonary tuberculosis, hepatitis B (with HBV-DNA < 500IU/ml and normal liver function after treatment can be enrolled), hepatitis C virus positive, uncorrectable electrolyte disorders, uncontrollable pericardial effusion, pleural effusion and ascites, etc.; (11) Allergic to any drug in this protocol; (12) Within 14 days before entry, used immunosuppressive drugs or corticosteroids > 10mg/day prednisone at the efficacy dose; (13) Within 4 weeks before entry, received radiotherapy, chemotherapy, targeted therapy or immunotherapy; (14) Pregnant or lactating women; The researchers considered those who were not suitable for inclusion in the study.

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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: Vibecototamab combined with Putilimab; This study is a single-arm, prospective, phase II clinical trial, aiming to enroll patients with advanced biliary system tumors who have failed at least one line of standard treatment and are positive for EGFR.

Drug: Vibecotecotamab combined with Putilimab for EGFR-positive refractory biliary malignant tumors; This study is a single-arm, prospective, phase II clinical trial, aiming to enroll patients with advanced biliary system tumors who have failed at least one line of standard treatment and are positive for EGFR. After the subjects sign the informed consent, those who are confirmed to meet the inclusion criteria undergo treatment with puzelimab, 200mg per dose, intravenous infusion on D1, once every 3 weeks; vibercept, 2.0mg/kg, intravenous infusion on D1, once every 3 weeks. The combination therapy will continue until disease progression or intolerable side effects occur.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate (ORR)	Description: The total number of participants in the intention-to-treat (ITT) population who achieve a complete response (CR) or partial response (PR) will be considered valid, and the statistical results were used to calculate the ORR based on imaging (CT/MRI) using the RECIST v1.1 criteria.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free survival (PFS): It refers to the period from the first day of using the study drug until the first radiological assessment of disease progression (PD) or death due to any cause. If the subject does not experience PD or death by the study's cut-off date, or has received other anti-tumor treatment, the last efficacy assessment result before the cut-off date or the start date of other anti-tumor treatment (whichever occurs first) will be used as the censored time.	Up to 2 years
Disease Control Rate (DCR)	The percentage of cases that achieved remission and stable lesion after treatment among all the evaluable cases.	Up to 2 years
Overall Survival (OS)	It refers to the period from the day the research drug was first used until death occurred for any reason. The end For the subjects who were still alive at the next follow-up, their OS was defined as data censored based on the last follow-up time. For the subjects who were lost to follow-up, their OS was defined as data censored based on the last confirmed survival time before the loss. The definition of censored OS is the time from enrollment to censoring.	Up to 2 years

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): February 29, 2028

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2026（225）

Drug and device information, study documents

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