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PIPELINE > TRIAL OVERVIEW

Trial Information
Molecule Overview
KRAS G12D Inhibitor
LY3962673
KRAS G12D MoA

Kano Y1; Hofmann MH2; Ostrem JML and Shokat KM3; Gong X4; Iyer C5

Target

KRAS is one of the most frequently mutated oncogenes.6 Among the various KRAS mutations, G12D is the most prevalent, occurring in 37.0% of pancreatic cancer cases, 12.5% of colorectal cancer cases, and 4.9% of non-small cell lung cancer cases.2 KRAS G12D mutations also confer a worse prognosis when compared to KRAS-wildtype tumors.7,8

Molecule

LY3962673 is a selective, oral, non-covalent KRAS G12D inhibitor.4 Scientists have observed preclinical dose-dependent tumor growth inhibition as monotherapy and in combination with other medicines.4 LY3962673 is also selective against HRAS, NRAS, non-mutated KRAS, and other non-G12D-mutant KRAS.5

Clinical Development

LY3962673 is being studied in patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, and other solid tumors with a KRAS G12D mutation.9

References

  1. Kano Y, et al. Nat Comm. 2019;10(1):224.
  2. Hofmann MH, et al. Cancer Discov. 2022;12(4):924-937.
  3. Ostrem JML, Shokat KM. Nat Rev Drug Discov. 2016;15(11):771-785.
  4. Gong X, et al. LY3962673, an oral, highly potent, mutant-selective, and non-covalent KRAS G12D inhibitor demonstrates robust anti-tumor activity in KRAS G12D models. Presented at: AACR Annual Meeting; April 5-10, 2024; San Diego, CA. Poster #3316.
  5. Iyer C, et al. Preclinical characterization of LY3962673, an orally bioavailable, highly potent, and selective KRAS G12D inhibitor. Presented at: AACR-NCI-EORTC Annual Meeting; October 11-15, 2023; Boston, MA. Poster B115.
  6. Kim D, et al. Nature. 2023;619(7968):160-166.
  7. Bournet B, et al. Clin Transl Gastroenterol. 2016;7(3):e157.
  8. Ricciuti B, et al. Ann Oncol. 2022;33(10):1029-1040.

  9. A Phase 1a/1b Trial of LY3962673 in Participants With KRAS G12D-Mutant Solid Tumors. ClinicalTrials.gov identifier: NCT06586515. Updated November 18, 2024. Accessed November 20, 2024. https://clinicaltrials.gov/study/NCT06586515

For information on trial enrollment, locations, and more, call 1-800-545-5979.
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or visit www.clinicaltrials.gov for more information on this trial