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PIPELINE > TRIAL OVERVIEW

Trial Information
Molecule Overview
Nectin-4 Antibody-Drug Conjugate 2
LY4052031
Nectin 4 LNC MOA

Dumontet C, et al1; Challita-Eid PM, et al2; Heath EI and Rosenberg JE3; Sagar D, et al4

Target

Nectin-4 is a type I transmembrane protein and a member of the nectin glycoprotein family.3 Nectin-4 is primarily expressed in the placenta during fetal development and is weakly expressed in some adult human tissues, such as skin.3,5 Overexpression of Nectin-4 has been observed in several solid tumor types including urothelial, breast, cervix, lung, and ovarian cancers,2,5 and is associated with promoting tumor proliferation and metastasis.3 The higher expression of Nectin-4 in tumor cells compared to normal cells makes the protein an ideal target for tumor specific delivery of cytotoxic agents via an antibody-drug conjugate (ADC).3

Molecule

LY4052031 is a next-generation anti-Nectin-4 targeting ADC. It is comprised of a human IgG1 Fc-silent monoclonal Nectin-4 antibody linked to a novel camptothecin (topoisomerase I inhibitor) payload, via a cleavable linker with a homogeneous drug-antibody ratio (DAR) of 8:1. In preclinical in vivo models, LY4052031 has shown antitumor activity across a range of Nectin-4 expression levels, including a Nectin-4 MMAE ADC-resistant model.4

Clinical Development

LY4052031 is being investigated in a global open-label, multicenter, phase 1a/1b study in patients with advanced or metastatic urothelial carcinoma and other select solid tumors.

References

  1. Dumontet C, et al. Nat Rev Drug Discov. 2023;22(8):641–661.

  2. Challita-Eid PM, et al. Cancer Res. 2016;76(10):3003-3013.

  3. Heath EI, Rosenberg JE. Nat Rev Urol. 2021;18(2):93-103.

  4. Sagar D, et al. A next generation treatment for Nectin-4 positive cancers: preclinical characterization of LY4052031, an anti-Nectin-4 antibody, conjugated to a novel camptothecin payload. Presented at: AACR Annual Meeting; April 8, 2024; San Diego, CA.

  5. Fares J, et al. Preclinical characterization of LY4101174, a next-generation antibody drug conjugate (ADC) targeting Nectin-4. Poster presented at: AACR-NCI-EORTC Annual Meeting; October 11-15, 2023; Boston, MA.

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