Phase II Study of Osimertinib (AZD9291) in Advanced Non-Small Cell Lung Cancer Patients with Exon 20 Insertion Mutations in EGFR

By Zofia Piotrowska, MD, MHS

Every year, over 220,000 Americans are affected by non-small cell lung cancer (NSCLC), and NSCLC is the leading cause of cancer-related deaths in the US. About 10-15% of these patients have a mutation in the epidermal growth factor receptor (EGFR) gene that can be targeted to treat their NSCLC. New therapies such as erlotinib, gefitinib, and afatinib, which target this mutation, have improved treatment response rates and progression-free survival (PFS) compared to the previous standard-of-care chemotherapy.

Unfortunately, resistance to these treatments typically develops after about one year. Osimertinib is a relatively new drug that is now FDA-approved for NSCLC cancers with certain types of EGFR mutations that have developed resistance to other treatments. However, osimertinib has not been tested among patients with less common EGFR mutations such as exon 20 insertion.

EA5162 is a single-arm phase 2 trial that aims to evaluate the best objective response rate of osimertinib among patients with advanced NSCLC with EGFR exon 20 insertion mutations. The study’s secondary endpoints include determining the PFS and overall survival (OS) in these patients, as well as the safety profile of 160 mg daily dosing of osimertinib.

EA5162 has no restrictions on the maximum number of prior therapies allowed. Patients who have already received other exon 20-directed therapies are eligible for EA5162. Patients must have received at least one prior line of therapy for this cancer (and must not have previously received osimertinib).

Other eligibility criteria include:

• Advanced disease: either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease
• An EGFR exon 20 insertion mutation, detected by any Clinical Laboratory Improvement Act (CLIA)-certified tissue assay
• Measurable disease
• No previous treatment targeting PD-L1, PD-1 or CTLA-4 within 6 months prior to registration

EA5162 is an important study that has the potential to prolong survival and change the standard of care in a subset of patients with NSCLC. With a current enrollment of 28 participants, the trial is continuing to accrue toward its goal of 46 participants.

Learn more about EA5162 at ecog-acrin.org.

Dr. Piotrowska (Massachusetts General Hospital Cancer Center) is the study chair for this trial. The study co-chair is Lecia Sequist, MD, MPH (Massachusetts General Hospital Cancer Center).