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PIPELINE > TRIAL OVERVIEW

NCT06607185

NSCLC | Pancreatic Ductal Adenocarcinoma | Colorectal Cancer | Other Solid Tumors

Trial Information
Molecule Overview
Pan-KRAS Inhibitor
LY4066434
Pan-KRAS Inhibitor

Kano Y1; Hofmann MH2; Ostrem JML and Shokat KM3; Prieto L4

Target

KRAS is among the most frequently mutated oncogenes with multiple subtypes conferring a worse clinical prognosis.2,5,6 While KRAS G12C inhibitors have received regulatory approval in certain countries, a significant unmet need persists for other KRAS mutant alleles, such as KRAS G12D, G12V, and G13D, which account for over 100,000 annual diagnoses in the United States alone.2 Additionally, there are no selective targeted agents in clinical development for several less common KRAS mutations such as G12A and G12S.

Molecule

LY4066434 is an oral, non-covalent, pan-KRAS inhibitor.4 In preclinical studies, scientists have observed that LY4066434 inhibition includes, but is not limited to, KRAS G12D, G12V, G12C, G13D, G12A, and G12S. Inhibition also includes wildtype KRAS, while sparing HRAS and NRAS.4

Clinical Development

LY4066434 is being studied in patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, and other solid tumors who have qualifying KRAS mutations.7

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. Prieto L, et al. Preclinical characterization of orally bioavailable, highly potent pan-KRAS inhibitors with selectivity over HRAS and NRAS. Presented at: AACR-NCI-EORTC Annual Meeting; October 11-15, 2023; Boston, MA. Poster B116.
  5. Kim D, et al. Nature. 2023;619(7968):160-166.
  6. Zhu G, et al. Mol Cancer. 2021;20(1):143.
  7. A Phase 1a/1b Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors. ClinicalTrials.gov identifier: NCT06607185. Updated November 12, 2024. Accessed November 20, 2024. https://clinicaltrials.gov/study/NCT06607185
For information on trial enrollment, locations, and more, call 1-800-545-5979.
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