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

Recruiting

• Conditions: Biliary Tract Cancer; Cholangiocarcinoma
• Interventions: Drug: lenvatinib plus pembrolizumab

• Registration Number: NCT06648057
• Lead Sponsor: CHA University

Brief Summary

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.

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 Timeline

• Study Start: 2024-09-23
• Status Verified: 2024-10
• Study First Submitted: 2024-10-07
• Study First Submitted QC: 2024-10-17
• Last Update Submitted: 2024-10-17
• Study First Posted: 2024-10-18
• Last Update Posted: 2024-10-18
• Primary Completion: 2026-09-23
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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.

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Len/Pemb	lenvatinib plus pembrolizumab	lenvatinib plus pembrolizumab combination therapy.

Primary Outcome Measures

Name	Time	Method
collected tumor samples	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.
Collected Blood Samples	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 Outcome Measures

Name	Time	Method
Multi-Omics Analysis for Therapeutic Target Identification	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).
Biomarkers on the Efficacy of Lenvatinib and Pembrolizumab for Advanced Biliary Tract Cancer	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.

Trial Locations

Locations (1)

Bundang CHA Medical Center; 🇰🇷 Seongnam-si, Gyeonggi-do, Korea, Republic of