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bempegaldesleukin + nivolumab + cabozantinib
- Development stage
- Discontinued
- Lead developer
- Nektar Therapeutics
- Modality
- Small Molecules, Monoclonal Antibodies → Antibody-Based Therapeutics, Cytokines & Interferons → Recombinant Proteins and Enzymes
- Administration
- Intravenous, Oral
01
Overview
This combination consists of three agents: - **Bempegaldesleukin (NKTR-214, BEMPEG)**: a pegylated interleukin-2 (IL-2) cytokine prodrug designed to selectively activate and expand effector CD8+ T cells and natural killer cells in the tumor microenvironment, enhancing antitumor immunity while minimizing toxicity. - **Nivolumab (Opdivo, BMS-936558)**: a monoclonal antibody that inhibits the programmed cell death protein 1 (PD-1) immune checkpoint, restoring T cell activity and allowing the immune system to target cancer cells. - **Cabozantinib (Cabometyx, XL184)**: an orally administered small molecule tyrosine kinase inhibitor that targets multiple kinases, including VEGFR, MET, and AXL, involved in tumor angiogenesis and progression. The combination was investigated as first-line therapy for advanced or metastatic renal cell carcinoma (RCC), aiming to synergize immune activation (IL-2 pathway, checkpoint inhibition) with blockade of tumor proliferation and angiogenesis (TKI mechanism). Clinical development was discontinued after failure to demonstrate benefit in pivotal trials.
- Other names
- bempegaldesleukin + nivolumab + cabozantinib
02
Targets
KIT (c-KIT proto-oncogene receptor tyrosine kinase)IL2RA (Interleukin-2 receptor alpha subunit)VEGFR4 (Vascular endothelial growth factor Receptor-3)VEGFR2 (Vascular endothelial growth factor receptor 2)FLT3 (Fms related receptor tyrosine kinase 3)AXL (AXL receptor tyrosine kinase)MET (Mesenchymal-epithelial transition factor receptor)TEK (Tie2)VEGFR-1 (Vascular endothelial growth factor receptor 1)RET (Rearranged during transfection receptor tyrosine kinase)IL2RB (IL-2 receptor beta chain)PDCD1 (Programmed cell death protein 1 receptor)
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