Oncology Pipeline

For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. In 2019 Lilly created Loxo Oncology at Lilly, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new medicines that work in early clinical development and will matter to patients.

PDGFRα Antibody

Olaratumab, LY3012207, IMC‑3G3

Heldin CH, et al¹

Target

Platelet-derived growth factor receptor α (PDGFRα) is expressed in multiple tumor types, and its aberrant activation has been implicated in cancer. Coexpression of PDGFRα and PDGFs, consistent with autocrine-mediated growth, has been reported in sarcomas and glioblastomas.² Gene amplification and activating mutations of PDGFRα have been found in subsets of glioblastomas, non-small cell lung cancers, and gastrointestinal stromal tumors.^2,3 PDGFRα expression has been associated with increased metastatic potential in preclinical models.^4,5 Paracrine stimulation of PDGFRα-positive lung stromal cells has been shown in preclinical studies to potentially support new lesion development in the lung.^6-8

Molecule

Olaratumab (LY3012207, IMC-3G3) is a human IgG1 monoclonal antibody that has been shown in vitro to bind to human PDGFRα with high affinity and block PDGF-AA, PDGF-BB, and PDGF-CC ligands from binding to the receptor.^9,10

Clinical Development

Olaratumab is being investigated in clinical trials in patients with pancreatic cancer or sarcoma.

References

Heldin CH, et al. Biochim Biophys Acta. 1998;1378(1):F79-F113.
Ostman A, Heldin CH. Adv Cancer Res. 2007;97:247-274.
Ramos AH, et al. Cancer Biol Ther. 2009;8(21):2042-2050.
Fitzer-Attas CJ, et al. Oncogene. 1997;15(13):1545-1554.
Dolloff NG, et al. Oncogene. 2005;24(45):6848-6854.
Dong J, et al. EMBO J. 2004;23(14):2800-2810.
Campbell JS, et al. Proc Natl Acad Sci USA. 2005;102(9):3389-3394.
LeBlanc A, et al. AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; October 26-30, 2017; Philadelphia, PA. Abstract LBB01.
Loizos N, et al. Mol Cancer Ther. 2005;4(3):369-379.
Data on file, Eli Lilly and Company. ONC20150219A.

The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.

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