AZD9291, an investigational third-generation EGFR inhibitor being researched by AstraZeneca scientists, seems to successfully target both the activating and resistance mutant forms of EGFR more potently than normal EGFR, according to study results presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

This is good news for the patients with non-small cell lung cancer (NSCLC) who have mutations in the growth factor gene EGFR whose disease has developed a resistance to the EGFR inhibitor drugs erlotinib and gefitinib. In many cases, this is due to the cancer cells acquiring a second mutation called EGFR T790M, also known as the “resistance mutation.”

The new EGFR kinase inhibitor, AZD9291, has proven to be highly active in preclinical models and is well tolerated in animal models, inhibiting both activating and resistant EGFR mutations while sparing the normal form of EGFR that is present in normal skin and gut cells, thereby reducing the side effects encountered with currently available medicines, according to researchers.

“Findings from preclinical studies have recently been translated to the clinic, where the drug has already demonstrated tumor shrinkage in patients and has been well tolerated, with low rates of side effects,” said Susan Galbraith, MD, PhD, head of the Oncology Innovative Medicines Unit at AstraZeneca.
“The degree of response to treatment with AZD9291 in such a short period of time is very exciting. This new drug has the potential to provide new treatment options for patients in this setting.”