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yttrium-90 microspheres + nivolumab + ipilimumab + lenvatinib

Development stage
Unknown
Lead developer
West China Hospital of Sichuan University
Modality
Small Molecules, Antibody-Radionuclide Conjugates → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Intra-arterial, Intravenous, Oral
01

Overview

This quadruple combination therapy is being investigated for the treatment of unresectable hepatocellular carcinoma (HCC). It integrates Selective Internal Radiation Therapy (SIRT) using yttrium-90 (Y90) microspheres with a dual immune checkpoint inhibitor regimen (nivolumab and ipilimumab) and a multi-kinase inhibitor (lenvatinib). Y90 microspheres are administered intra-arterially to provide localized beta radiation, which induces tumor necrosis and immunogenic cell death. Nivolumab and ipilimumab are monoclonal antibodies that block the PD-1 and CTLA-4 pathways, respectively, to enhance systemic T-cell activation against tumor cells. Lenvatinib is an oral small molecule that inhibits multiple receptor tyrosine kinases, including VEGFR1-3 and FGFR1-4, thereby suppressing tumor angiogenesis and proliferation. This multi-modal approach, led by West China Hospital, aims to leverage the potential synergy between local radiation, systemic immunotherapy, and anti-angiogenic therapy to improve outcomes in patients with advanced HCC.

Other names
Y90-SIRT + nivolumab + ipilimumab + lenvatinibY90 + Nivo + Ipi + Len
02

Targets

FGFR4 (Fibroblast growth factor receptor 4)PDCD1 (Programmed cell death protein 1 receptor)PDGFRA (Platelet-derived growth factor receptor alpha)KIT (c-KIT proto-oncogene receptor tyrosine kinase)VEGFR2 (Vascular endothelial growth factor receptor 2)FGFR3 (Fibroblast growth factor receptor 3)CTLA-4 (Cytotoxic t-lymphocyte–associated protein 4)VEGFR-1 (Vascular endothelial growth factor receptor 1)DNAVEGFR3 (Vascular endothelial growth factor receptor 3)FGFR2 (Keratinocyte growth factor receptor)FGFR1 (Fibroblast growth factor receptor 1)RET (Rearranged during transfection receptor tyrosine kinase)

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