PIPELINE > TRIAL OVERVIEW

FRα Antibody-Drug Conjugate
LY4170156
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Bax HJ, et al1; Scaranti M, et al2; Kalli KR, et al3; Viricel W, et al4

Target

Folate receptor alpha (FRα) is a cell-surface glycoprotein encoded by the gene FOLR1. It binds to folic acid and reduced folates with high affinity.1,2 Upon binding, the receptor-ligand complex is internalized via potocytosis and fused with a lysosome, releasing the folate for use in reactions.2 The expression of FRα in non-malignant tissues is limited, whereas it is overexpressed in many solid tumors such as ovarian, non-small cell lung, and colorectal cancers, making the receptor an attractive therapeutic target for these indications.1,4

Molecule
LY4170156 is an FRα-targeting antibody-drug conjugate (ADC) composed of an Fc-silenced, humanized IgG1 monoclonal antibody, a proprietary polysarcine hydrophobicity masking agent with a dipeptide cleavable linker, and the topoisomerase I inhibitor payload exatecan. It has a drug-antibody ratio (DAR) of 8. In preclinical models, LY4170156 has shown activity against a range of FRα-expressing tumors, including low and moderate FRα-expressing ovarian tumors as well as other solid tumors.4
Clinical Development

LY4170156 is being studied in ovarian and endometrial cancers, as well as other FRα-expressing solid tumors, in a phase 1 study.

References

  1. Bax HJ, et al. Br J Cancer. 2023;128(2):342-353.
  2. Scaranti M, et al. Nat Rev Clin Oncol. 2020;17(6):349-359.
  3. Kalli KR, et al. Gynecol Oncol. 2008;108(3):619-626.
  4. Viricel W, et al. Cancer Res. 2023;83(suppl 7):1544.
Clinical Development

LY4170156 is being studied in ovarian and endometrial cancers, as well as other FRα-expressing solid tumors, in a phase 1 study.

References

  1. Bax HJ, et al. Br J Cancer. 2023;128(2):342-353.
  2. Scaranti M, et al. Nat Rev Clin Oncol. 2020;17(6):349-359.
  3. Kalli KR, et al. Gynecol Oncol. 2008;108(3):619-626.
  4. Viricel W, et al. Cancer Res. 2023;83(suppl 7):1544.
For information on trial enrollment, locations, and more, call 1-800-545-5979.