Drug intelligence / Profile preview

loxo-435 + pembrolizumab + enfortumab vedotin

Development stage
Unknown
Lead developer
Eli Lilly
Modality
Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Intravenous
01

Overview

This is a combination of three agents under evaluation primarily for the treatment of urothelial carcinoma. - **LOXO-435** is a small molecule selective inhibitor of fibroblast growth factor receptor 3 (FGFR3), developed for FGFR3-altered cancers, especially urothelial carcinoma. - **Pembrolizumab** is a monoclonal antibody targeting programmed cell death protein 1 (PD-1), serving as an immune checkpoint inhibitor to activate T-cell responses against tumor cells. - **Enfortumab vedotin** is an antibody-drug conjugate targeting Nectin-4, highly expressed on urothelial carcinoma cells. It consists of a monoclonal antibody (enfortumab) linked to a cytotoxic agent (monomethyl auristatin E, MMAE), which disrupts microtubule assembly and induces apoptosis upon internalization[1][2][4][5]. This multi-agent combination is investigated to exploit synergy between FGFR3 blockade, immune checkpoint inhibition, and targeted cytotoxic delivery, mainly for metastatic or locally advanced urothelial carcinoma in clinical studies.

Brand names
Padcev (enfortumab vedotin)Keytruda (pembrolizumab)
Other names
enfortumab vedotin-ejfvAGS-22M6E (enfortumab vedotin)
02

Targets

PVRL4 (Nectin cell adhesion molecule 4)FGFR3 (Fibroblast growth factor receptor 3)PDCD1 (Programmed cell death protein 1 receptor)TUBB (Tubulin (alpha and beta subunits))

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