PIPELINE > TRIAL OVERVIEW

Nectin-4 Antibody-Drug Conjugate
ETx-22, LY4101174
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Dumontet C, et al1; Challita-Eid PM, et al2; Heath EI and Rosenberg JE3; Fares J, et al4

Target

Nectin-4 is a type I transmembrane protein and a member of the nectin glycoprotein family.Nectin-4 is primarily expressed in the placenta during fetal development and is weakly expressed in some adult human tissues, such as skin.3,4 Overexpression of nectin-4 has been observed in several solid tumor types including urothelial, breast, cervix, lung, and ovarian cancers,2,4 and is associated with promoting tumor proliferation and metastasis.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
LY4101174 is a next-generation anti-nectin-4 targeting ADC. It is comprised of a humanized IgG1 Fc-silent monoclonal nectin-4 antibody linked to the topoisomerase 1 inhibitor, exatecan, via a maleimide-B-glucuronide poly-sarcosine linker with a homogeneous drug-antibody ratio (DAR) of 8. In preclinical in vivo models, LY4101174 has shown anti-tumor activity across a range of nectin-4 expression levels including a nectin-4 MMAE ADC resistant model.
Clinical Development

LY4101174 is being investigated in a global open-label, multicenter, phase 1a/1b study in patients with advanced or metastatic urothelial carcinoma and 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. Fares J, et al. Preclinical characterization of ETx-22 (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.
Clinical Development

LY4101174 is being investigated in a global open-label, multicenter, phase 1a/1b study in patients with advanced or metastatic urothelial carcinoma and 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. Fares J, et al. Preclinical characterization of ETx-22 (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.
For information on trial enrollment, locations, and more, call 1-800-545-5979.