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zanzalintinib + AB521 + nivolumab

Development stage: Unknown
Lead developer: Exelixis
Modality: Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration: Oral, Intravenous

Overview

A novel **triplet investigational combination** of zanzalintinib (XL092), AB521, and nivolumab designed for advanced clear cell renal cell carcinoma or other advanced solid tumors. Zanzalintinib is a small molecule multi-targeted tyrosine kinase inhibitor, AB521 is a small molecule hypoxia-inducible factor 2 alpha (HIF-2α) inhibitor, and nivolumab is a monoclonal antibody immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1). The combination aims to provide antitumor activity through complementary mechanisms: direct tumor cell inhibition (zanzalintinib), disruption of HIF-2α-mediated transcriptional programs (AB521), and enhancement of immune-mediated tumor cell killing (nivolumab). Clinical investigation is ongoing to determine recommended dosing, safety, pharmacokinetics, and preliminary efficacy in advanced solid tumors, primarily renal cell carcinoma[1][2][3][4].

Other names: zanzalintinib + AB521 + nivolumab

Targets

EPAS1 (Hypoxia-inducible factor 2-alpha)AXL (AXL receptor tyrosine kinase)PDCD1 (Programmed cell death protein 1 receptor)MET (Mesenchymal-epithelial transition factor receptor)VEGFR2 (Vascular endothelial growth factor receptor 2)

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