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

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.

Timeline

Start

2021-09-15

Primary completion

2025-07-18

Completion

2025-12-02

Drugs

Indications