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NCT Number: NCT06648057

Investigation of Predictive Biomarkers in Patients With Advanced BTC 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.

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Key information

Conditions

Biliary Tract Cancer Adenocarcinoma Biliary Tract Diseases Biliary Tract Neoplasms Carcinoma Cholangiocarcinoma Digestive System Diseases Digestive System Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

20 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Bundang CHA Medical Center

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location status: Recruiting

Location contact

Hong Jae Chon, MD. PhD

CONTACT

[email protected]

82-31-780-3928

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Lenvatinib plus Pembrolizumab

Drug
  • 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

Primary outcomes

  1. 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.

  2. 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).

Secondary outcomes

  1. 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).

  2. 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.

Other outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Hong Jae Chon, MD. PhD

CONTACT

[email protected]

82-31-780-3928

Sponsors and collaborators

Lead sponsor

CHA University

Other

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Oct 18, 2024
Registry last updated
Mar 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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