Drug intelligence / Profile preview

sitravatinib + pembrolizumab + enfortumab vedotin

Development stage
Discontinued
Lead developer
Bristol Myers Squibb
Modality
Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Oral, Intravenous
01

Overview

**sitravatinib + pembrolizumab + enfortumab vedotin** is an investigational combination regimen comprising three distinct oncology agents: - **Sitravatinib** is a spectrum-selective receptor tyrosine kinase inhibitor (RTKI), targeting the TAM family (TYRO3, AXL, MER), split kinase family receptors, and several other RTKs. It acts by blocking pathways implicated in resistance to checkpoint inhibitors and modulating the tumor microenvironment to enhance anti-tumor immunity. - **Pembrolizumab** is a humanized monoclonal antibody directed against programmed cell death protein 1 (**PD-1**) receptor. By blocking PD-1, it enhances the immune system’s ability to detect and destroy tumor cells (checkpoint inhibitor). - **Enfortumab vedotin** is an antibody-drug conjugate (ADC) targeting **Nectin-4** on tumor cells, delivering the cytotoxic microtubule-disrupting agent monomethyl auristatin E (MMAE) to induce tumor cell apoptosis. This combination is primarily being explored for advanced or metastatic urothelial carcinoma, especially in patients previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy. It aims to overcome resistance to immunotherapies and expand treatment options in cisplatin-ineligible and treatment refractory populations[2][5].

02

Targets

ABCG2 (Breast cancer resistance protein)AXL (AXL receptor tyrosine kinase)VEGFR2 (Vascular endothelial growth factor receptor 2)KIT (c-KIT proto-oncogene receptor tyrosine kinase)MET (Mesenchymal-epithelial transition factor receptor)PVRL4 (Nectin cell adhesion molecule 4)PDCD1 (Programmed cell death protein 1 receptor)RET (Rearranged during transfection receptor tyrosine kinase)

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