Investigation of Predictive Biomarkers in Patients With Advanced BTC Treated With Lenvatinib Plus Pembrolizumab

March 17, 2026 updated by: Hong Jae Chon, CHA University

Investigation of Predictive Biomarkers in Patients With Advanced Biliary Tract Cancer Treated With Lenvatinib Plus Pembrolizumab

The goal of this observational study is to evaluate the clinical efficacy and safety of lenvatinib plus pembrolizumab combination therapy in patients with advanced biliary tract cancer (BTC). This study aims to identify potential biomarkers that may predict treatment response by analyzing genetic data from blood and tissue samples. The study will focus on real-world clinical outcomes and the exploratory discovery of biomarkers associated with the efficacy of this treatment regimen.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Biliary tract cancers (BTCs) have a higher prevalence in Asia compared to Western countries, with South Korea ranking second globally in BTC incidence. According to data from the Central Cancer Registry in 2023, the 5-year survival rate for BTC from 2017 to 2021 was 28.9%, significantly lower than other cancers such as gastric cancer (77.9%), colorectal cancer (74.3%), and breast cancer (93.8%).

Surgery is the primary treatment for BTC, but only 40-50% of patients are eligible for curative resection. For patients with unresectable, advanced, or metastatic BTC, the standard first-line treatment has been gemcitabine plus cisplatin (GP) since the results of the ABC-02 Phase 3 trial in 2010. Recently, two Phase 3 trials-TOPAZ-1 in 2022 and KEYNOTE-966 in 2023-demonstrated significant survival benefits with the addition of immune checkpoint inhibitors (durvalumab or pembrolizumab) to GP therapy, establishing these combination regimens as the new first-line standard treatment for advanced BTC. These combinations have been approved for use in South Korea.

However, for patients who fail first-line GP therapy, the most commonly selected second-line treatment, FOLFOX (5-FU + leucovorin + oxaliplatin), offers only a modest survival extension of about one month compared to supportive care. This highlights the clinical unmet need for more effective second-line treatments. A multicenter Phase 2 trial has demonstrated the efficacy of lenvatinib plus pembrolizumab as a promising treatment option for these patients.

This prospective observational study aims to evaluate the clinical efficacy and safety of lenvatinib plus pembrolizumab combination therapy in real-world clinical practice for advanced BTC. Additionally, the study seeks to explore potential predictive biomarkers through genetic analyses of blood and tissue samples to better understand which patients are most likely to benefit from this treatment.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • South Korea
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, South Korea, 13496
        • Recruiting
        • Bundang CHA Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with Advenced Biliary Tract Cancer will be recruited at CHA Bundang Medical Center

Description

Inclusion Criteria:

  • Patients with histologically or cytologically confirmed advanced biliary tract cancer.
  • Patients scheduled to receive Lenvatinib + Pembrolizumab for the treatment of advanced biliary tract cancer.
  • ECOG performance status of 0-2.
  • Patients aged 20 years or older at the time of treatment initiation.
  • Patients who understand and consent to participate in this study, and agree to provide samples obtained during the examination process.

Exclusion Criteria:

  • Patients who do not consent to participate in the study or withdraw their consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Len/Pemb
lenvatinib plus pembrolizumab combination therapy.
Drug: lenvatinib plus pembrolizumab
  • The collection of peripheral blood samples will follow the schedule below (20 cc per collection, up to 5 times):
  • Before systemic therapy, at 3 weeks after starting systemic therapy (Cycle 1), at 6 weeks (Cycle 2)
  • (If possible) at the time of confirmed partial response (1 time), and at the time of disease progression (1 time).
  • Additional tumor tissue samples will be collected only if possible, according to the following schedule:

If the patient undergoes surgery or additional biopsy related to treatment (collected from preserved specimens).

Other Names:
  • Liquid biopsy, RNA-sequencing, NGS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
collected tumor samples
Time Frame: through study competition, an average of 2 years
Tumor samples will be collected from patients with advanced biliary tract cancer. The incidence of genetic alterations in these samples will be analyzed using H&E staining, immunohistochemistry (IHC), and RNA sequencing. The data will be reported as the percentage of patients with detectable genetic alterations and correlated with treatment response and survival duration.
through study competition, an average of 2 years
Collected Blood Samples
Time Frame: Through study completion, an average of 2 years
Blood samples will be collected from patients with advanced biliary tract cancer.These samples will undergo flow cytometry, ELISA, and ctDNA analysis, and the results will be correlated with treatment response and survival outcomes. (PFS, OS).
Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Multi-Omics Analysis for Therapeutic Target Identification
Time Frame: Through study completion, an average of 2 years.
Multi-omics analysis, including DNA, RNA, and protein analysis, will be conducted to identify potential therapeutic targets and subtypes of biliary tract cancer. The analysis will integrate molecular data to identify actionable genetic alterations and protein expression levels, which will be summarized and correlated with clinical outcomes (e.g., PFS, OS).
Through study completion, an average of 2 years.
Biomarkers on the Efficacy of Lenvatinib and Pembrolizumab for Advanced Biliary Tract Cancer
Time Frame: Through study completion, an average of 2 years.
his outcome will investigate the correlation between molecular biomarkers and the efficacy of lenvatinib and pembrolizumab in patients with advanced biliary tract cancer. Biomarkers will be evaluated for their association with overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). The outcome will report which biomarkers predict better therapeutic response.
Through study completion, an average of 2 years.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Through study completion, an average of 2 years.
This outcome measures the time from the start of treatment to the first occurrence of disease progression or death. PFS will be analyzed using Kaplan-Meier survival curves, and the median PFS will be reported.
Through study completion, an average of 2 years.
Overall Survival (OS)
Time Frame: Through study completion, an average of 2 years.
This outcome measures the time from the start of treatment to death from any cause. OS will be evaluated and reported using Kaplan-Meier survival analysis, and median OS will be calculated.
Through study completion, an average of 2 years.
Objective Response Rate (ORR)
Time Frame: Through study completion, an average of 2 years.
ORR is defined as the percentage of patients who achieve a complete or partial response based on RECIST 1.1 criteria. This outcome will report the proportion of patients who show a measurable response to treatment.
Through study completion, an average of 2 years.
Incidence of Adverse Events (AEs)
Time Frame: Through study completion, an average of 2 years.
The safety and tolerability of lenvatinib and pembrolizumab will be assessed by monitoring the occurrence and severity of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Through study completion, an average of 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CHA University

Investigators

  • Principal Investigator: Hong Jae Chon, MD. PhD, CHA University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2024

Primary Completion (Estimated)

September 23, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

October 7, 2024

First Submitted That Met QC Criteria

October 17, 2024

First Posted (Actual)

October 18, 2024

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 17, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHAMC 2024-08-040

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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