FDA Grants Osimertinib Accelerated Approval for T790M-Positive NSCLC

The new drug is indicated for use in patients who have progressed after another TKI.

The US Food and Drug Administration (FDA) granted accelerated approval to osimertinib (Tagrisso, AstraZeneca), previously known as AZD9291, for the treatment of advanced non–small-cell lung cancer (NSCLC) with the EGFR mutation T790M. The drug is indicated for use in patients who have progressed on or after use of another tyrosine kinase inhibitor (TKI).

“Our understanding of the molecular basis of lung cancer and reasons these cancers become resistant to prior treatments is rapidly evolving,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA, in a press release. “This approval provides a new treatment for patients who test positive for the EGFR resistance mutation, T790M, and is based on substantial evidence from clinical trials that shows Tagrisso had a significant effect on reducing tumor size in over half of patients who were treated.” 

The FDA also approved a companion diagnostic test, the cobas EGFR Mutation Test v2 (Roche). This is a new version of the test, that adds the T790M mutation to other known EGFR mutations.

Osimertinib’s approval is based on results from the AURA extension and AURA2 phase II trials, which collectively included 411 NSCLC patients who progressed after use of another TKI. In those trials together, the overall objective response rate (ORR) was 59%. In another phase I trial of the drug including 63 patients, the ORR was 51%, and the median duration of response was 12.4 months.

In the AURA and AURA2 trials, the most common adverse events (AEs) were generally mild or moderate and included diarrhea, rash, and dry skin. No grade 3 or higher AEs occurred in more than 3.5% of patients.

Though the FDA granted osimertinib accelerated approval, the drug is still being evaluated in a larger phase III trial (AURA3) comparing it to platinum-based doublet chemotherapy again in patients whose disease progressed with other TKI treatment and who harbor the T790M mutation. That study, which is active but not currently recruiting, has an estimated enrollment of 410 patients.

“This treatment has the potential to become the standard of care for patients living with EGFRm T790M non-small cell lung cancer,” said Pasi A Jänne, MD, PhD, of Harvard Medical School, in a press release from AstraZeneca. “The accelerated approval of AZD9291 highlights its clinical promise for a targeted group of patients and gives healthcare providers an important new option.”