Pembrolizumab in Combination With Lenvatinib in Patients With Advanced Biliary Tract Carcinoma

NCT04550624 | Completed Phase 2

• 1 other identifier: 2020-0001
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

The prognosis for unresectable and metastatic biliary tract cancers (BTCs) including cholangiocarcinoma is poor with first line gemcitabine and cisplatin offering a median overall survival of 11.7 months. There is no standard second- or third-line therapy for advanced BTC, and this represents an unmet medical need for novel therapies. The immune system plays a critical role in the development of Advanced Biliary Tract Carcinoma (BTC) and chronic inflammation is a common underlying risk factor for BTC. Vascular endothelial growth factor (VEGF) signaling in BTC may lead to an immune suppression via inadequate tumor antigen presentation and an impaired T cell-mediated immune response directed against tumor antigens. Lenvatinib significantly decreased the population of immunosuppressive tumor-associated macrophages and increased interferon-γ-producing cluster of differentiation 8+ (CD8+) T cells. Addition of programmed cell death protein 1 (PD-1)/programmed death-ligand (PD-L1) inhibitors helps reverse VEGF-mediated immune suppression, restore T cell function, and promote T cell tumor infiltration. The combination of lenvatinib and pembrolizumab has demonstrated promising activity with manageable adverse events in various solid tumor types. The investigators will assess the efficacy and safety of the combination of pembrolizumab and lenvatinib in patients with advanced BTC who failed standard therapy in this phase II study.

Conditions

Advanced Biliary Tract Carcinoma

Keywords

Advanced Biliary Tract Carcinoma; Pembrolizumab; Lenvatinib

Outcome Measures

Primary Outcomes (1)

• Evaluation of ORR

  Evaluate the objective response rate (ORR) (RECIST1.1) of lenvatinib in combination with pembrolizumab in patients with advanced BTC after progression on standard systemic therapies

  up to 36 months

Secondary Outcomes (7)

• All participants who receive at least one dose of study treatment will be evaluable for safety and tolerability through the monitoring of serious and non serious AEs, defined and graded according to NCI CTCAE v5.0.

  up to 36 months

• Duration of Overall Response (DOR)

  up to 36 months

• Progression-Free Survival (PFS)

  up to 36 months

• Overall Survival (OS)

  up to 36 months

• Objective Response Rate (ORR) of subgroups burden

  up to 36 months

Study Arms (1)

Interventional Arm

EXPERIMENTAL

This is an open-label, multi-center, phase II trial of lenvatinib in combination with pembrolizumab in patients with Advanced Biliary Tract Carcinoma (BTC) who have progressed on standard systemic therapy. All participants will be administered Pembrolizumab 200mg IV on day 1 and Lenvatinib 20mg PO daily days 1-21 of each cycle (21 days).

Drug: Pembrolizumab Injection [Keytruda]; Drug: Lenvatinib Mesylate

Interventions

Pembrolizumab Injection [Keytruda] DRUG

200mg IV on day 1 of each cycle

Also known as: Keytruda

Interventional Arm

Lenvatinib Mesylate DRUG

20mg PO daily days 1-21 of each cycle

Also known as: Lenvima

Interventional Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria in order to be eligible to participate in the study:
• Unresectable or metastatic, histologically-confirmed advanced BTC (excluding periampullary cancer)
• Failed standard systemic therapy for advanced BTC due to progression of disease or toxicity
• Measurable disease
• Prior chemoembolization, radiofrequency ablation, or radiation to the liver is allowed as long as the patient has measurable disease outside the chemoembolization or radiation area or measurable progression at the site of chemoembolization or radiation
• ECOG Performance status ≤ 1
• Life expectancy \> 3 months
• Adequate renal function as defined by Cr ≤ 1.5 upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2
• Adequate hepatic function as defined by bilirubin ≤ 2.5 x ULN and alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 5x ULN
• Adequate bone marrow reserve as evidenced by ANC \> 1500/mcl, Plts \>75,000/mcl, Hgb ≥ 9.0g/dl
• Prothrombin time / Partial thromboplastin time (PT/PTT) \<1.5x ULN
• Urine Protein: Creatinine ratio of \<1, if protein is \> 2+ on urinalysis
• Age ≥ 18 years
• Participants with past or ongoing hepatitis C virus (HCV) infection are eligible for the study. Treated participants must have completed their treatment at least 1 month prior to starting study intervention. Untreated or incompletely treated HCV participants may initiate anti-viral therapy for HCV if liver function remains stable for at least 3 months on study intervention
• Participants with controlled hepatitis B are eligible for the study, as long as they meet the following criteria:

You may not qualify if:

• Patients who exhibit any of the following conditions at screening will not be eligible to be enrolled to the study:
• Prior treatment with other VEGF-R directed therapies
• Periampullary cancer
• Major surgery or radiation within the 4 weeks prior to enrollment; is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of registration. The treated patients must recover from their relevant treatment(i.e. to≤1 grade or baseline) and from any AEs caused by any previous treatment
• Uncontrolled hypertension defined by systolic blood pressure (SBP)\>150 or diastolic blood pressure (DBP)\>90 despite titration of anti-hypertensive medications
• Active, known or suspected autoimmune disease
• Congestive heart failure or symptomatic coronary artery disease within 3 months prior to enrollment
• Cerebrovascular accident within prior 6 months
• Clinically significant hemorrhage, bleeding event, or thromboembolic disease within six months
• History of bowel perforation
• History of (non-infectious) pneumonitis that required steroids or currently has pneumonitis
• Known history of HIV infection
• Severely impaired lung function or history of interstitial lung disease
• Concurrent malignancy (other than adequately treated non-melanoma skin cancer, superficial transitional cell carcinoma of the bladder, and cervical CIS) diagnosed within the past 5 years or any currently active malignancy
• Positive serum pregnancy test within 72 hours of first dosing of study treatment

Sponsors & Collaborators

• Shanghai Jiahui International Hospital: lead
• Shanghai Zhongshan Hospital: collaborator

Study Sites (2)

Shanghai Jiahui International Hospital

Shanghai, Shanghai Municipality, 200233, China

Location

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, 200233, China

Location

MeSH Terms

Interventions

pembrolizumab; lenvatinib

Study Officials

• Andrew Zhu, PhD

  Shanghai JIH international Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: September 16, 2020
• Study Start: September 15, 2021
• Primary Completion: July 18, 2025
• Study Completion: December 2, 2025
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)