I have been the lead discovery scientist on an exciting project that aims to develop an anti-tumour compound for patients with non-small-cell lung cancer (NSCLC) and whose tumours have progressed despite therapy with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The discovery program rapidly delivered the candidate drug, AZD9291, through a fantastic cross-discipline project team effort. The success of the program was underpinned by the drive and motivation of the whole team.
Recently this project reached a significant milestone. AZD9291 completed early Phase I clinical activity and we’ve been reporting on the outcome during this week’s European Cancer Congress in Amsterdam. So far we are encouraged by these emerging phase I results for AZD9291, and while the compound is still in the early stages of development, we are now considering accelerating its development to try and meet this most pressing of patient needs.
Patients with NSCLC, which is associated with cancer-driving mutations in EGFR, often show an initial clinical response to the first generation reversible EGFR inhibitors that are currently available. However, the clinical efficacy of these agents is ultimately limited due to the emergence of drug resistance, which is often conferred by the gain of an additional EGFR T790M mutation that prevents drug inhibition. AZD9291 is an oral, selective, irreversible inhibitor of mutant EGFR. Our hope is that as an irreversible inhibitor, AZD9291 will overcome the acquired resistance that is often observed in these patients.
The development of this exciting program is another example from the growing oncology portfolio at AstraZeneca. It builds on the learning we have had from previous R&D projects in oncology and demonstrates that by understanding the mechanisms of resistance to currently effective therapies, we can innovate to improve the potential options for patients with cancer.
The focus in drug discovery is always on the benefit to the patient. This compound is being developed with that focus in mind – targeting tumours that are resistant to current EGFR inhibitor therapies. This is a significant unmet clinical need given that approximately half of patients with NSCLC are resistant to current therapies.
If the mechanism of action for AZD9291 is confirmed in future clinical trials then the compound may provide the foundation of a combination agent that is effective against cancers that have developed multiple resistance mutations. I look forward to championing this project through future clinical trials and gaining new insights and the scientific understanding that we hope can be applied in other areas of research.