The Efficacy and Safety of Pucotenlimab (PD-1) Combined With Becotatugvedotin (EGFR-ADC) in Advanced Cholangiocarcinoma

(1) Primary efficacy endpoint: Objective Response Rate (ORR) after 2 treatment cycles. ORR is defined as the proportion of subjects with complete response (CR) and partial response (PR) among all subjects. (2) Secondary efficacy endpoints include Progression-Free Survival (PFS), 2-year Relapse-Free Survival Rate, Disease Control Rate (DCR), Duration of Response (DOR), Adverse Reaction Incidence, 1-year Overall Survival Rate, 2-year Overall Survival Rate. Safety assessment includes physical examination, physical condition assessment (based on ECOG score), clinical laboratory tests and concomitant medication status. All observed drug toxicities and side effects need to be classified according to NCICTCAE and evaluated for their correlation with the drug. Patient Quality of Life (QoL) assessment uses the EORTC QLQC30 questionnaire and the BIL21 questionnaire. Recurrence patterns are classified as local recurrence and distant recurrence. Local control status is defined as the local failure rate (occurrence of local recurrence or local lymph node metastasis).

Study Overview

• Status: Not yet recruiting
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Drug: Vibecototamab（iv）+Putilimab（iv）

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mingyu Chen; Phone Number: +86 18757772223; Email: mychen@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1) Age ≥ 18 years old, both male and female are acceptable. 2) Histologically confirmed unresectable or metastatic cholangiocarcinoma (including: gallbladder cancer, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma), or (including: gallbladder cancer, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, after previous chemotherapy failure); 3) ECOG PS score 0-1. 4) Normal major organ functions, without severe blood, heart, lung, liver, kidney, bone marrow, or immune deficiency diseases.

  5) For female subjects of childbearing age, a pregnancy test (serum/urine) result must be negative within 14 days before enrollment, and they must voluntarily use appropriate methods of contraception during the observation period and 8 weeks after the last administration of the study drug; for male subjects, surgical sterilization or consent to use appropriate methods of contraception during the observation period and 8 weeks after the last administration of the study drug is required.

  6) IHC test is positive for EGFR. 7) Expected good compliance and able to follow up on efficacy and adverse reactions as per the protocol.

  8) Voluntary participation in this study and signing the informed consent form. If the subject is unable to read and sign the informed consent form due to lack of capacity, the guardian should act on behalf of the informed process and sign the informed consent form. If the subject is unable to read the informed consent form (such as illiterate subjects), a witness should witness the informed process and sign the informed consent form.

Exclusion Criteria:

• 1) Received PD1, PDL1, PDL2, CTLA4 treatment before enrollment, or directly received another stimulating or co-inhibitory T cell receptor (such as CTLA-4, OX40, CD137) treatment.

  2) Used any other study drug within 4 weeks before enrollment. 3) Has any active autoimmune disease or autoimmune disease history (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitaryitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (after hormone replacement therapy can be included)); has completely resolved childhood asthma and no need for any intervention after adulthood, and can be included, but patients requiring medical intervention with bronchodilators are not included.

  4) Has congenital or acquired immune dysfunction, such as human immunodeficiency virus (HIV) infection.

  5) Has uncontrolled clinical symptoms or diseases of the heart, such as NYHA II or above heart failure, unstable angina pectoris, heart attack within 1 year, patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.

  6) Had severe infection within 4 weeks before the first administration (such as requiring intravenous infusion of antibiotics, antifungal or antiviral drugs), or had unexplained fever > 38.5℃ during screening or before the first administration.

  7) Has a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.

  8) Had a live attenuated vaccine administered within 4 weeks before the first administration or is planned to be administered during the study period.

  9) Had other systemic malignant tumors within the last 5 years (excluding cured skin basal cell carcinoma and cervical carcinoma in situ and ovarian cancer).

  10) Has known allergies to any study drug. 11) Pregnant or lactating women, subjects with reproductive capacity who are unwilling to take effective contraceptive measures.

  12) Vulnerable groups other than the elderly or illiterate, including those with mental illness, cognitive impairment, critically ill patients, etc.

  13) Other situations considered by the investigator as not suitable for inclusion in this study. Such as: the patient already has central nervous system metastasis. There are serious laboratory test abnormalities, accompanied by factors related to family or society, which may affect the safety of the subjects or the collection of data/samples.

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: pucotenlimab（iv）+ Becotatugvedotin（iv）

Drug: Vibecototamab（iv）+Putilimab（iv）; Becotatugvedotin: 2mg/kg, intravenous, every 3 weeks, on day 1; pucotenlimab： 200mg, intravenous, every 3 weeks, on day 1 During administration, the pucotenlimab infusion should be completed at least 30 minutes before starting the Becotatugvedotin administration, via intravenous drip (60±10 minutes, the administration time for the first cycle should be ≥ 60 minutes). For patients who cannot tolerate the 60-minute infusion, the infusion time can be appropriately extended to 120 minutes. During the maintenance treatment phase, if any of the drugs is intolerable, another drug can be used for maintenance treatment. The investigator will assess whether to resume the medication based on the patient's recovery status. After 3-4 weeks after 3 courses, a re-examination and assessment will be conducted. For CR, PR, and SD, direct surgery will be performed. If PD, surgery or termination of the trial will be carried out.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR)	2 year

Secondary Outcome Measures

Outcome Measure	Time Frame
1-year overall survival rate	1 year
2-year disease-free survival rate	2 year
progression-free survival (PFS)	2 year
duration of response (DOR)	2 year
occurrence of adverse reactions	2 year
2-year overall survival rate	2 year

Collaborators and Investigators

• Sponsor: Sir Run Run Shaw Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 11, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma
• Other Study ID Numbers: SRRSH2025-0969

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