Pembrolizumab in Combination With Lenvatinib in Patients With Advanced Cholangiocarcinoma
Status:
Recruiting
Trial end date:
2025-12-01
Target enrollment:
Participant gender:
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 cholangiocarcinoma (CCA) and chronic
inflammation is a common underlying risk factor for CCA. Vascular endothelial growth factor
(VEGF) signaling in CCA 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 CCA who failed standard therapy in this phase II study.