FDA approves Tagrisso (AZD 9291, osimertinib) to treat EGFR T790M mutation positive NSCLC- AstraZeneca

AstraZeneca announced that the FDA has approved Tagrisso (osimertinib, formerly AZD 9291) 80 mg once-daily tablets for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.

Osimertinib is the only approved medicine indicated for patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer. This indication is approved under the FDA’s accelerated approval process based on tumour response rate and duration of response (DoR). Osimertinib is an EGFR-TKI, a targeted cancer therapy, designed to inhibit both the activating, sensitising mutations (EGFRm), and T790M, a genetic mutation responsible for EGFR-TKI treatment resistance. Nearly two-thirds of NSCLC patients who are EGFR mutation-positive and experience disease progression after being treated with an EGFR-TKI develop the T790M resistance mutation, for which there have been limited treatment options.

Continued approval for this indication may be contingent upon further confirmatory studies as it is an accelerated approval.

AstraZeneca has collaborated with Roche to develop the cobas EGFR Mutation Test v2 as the companion diagnostic for osimertinib. The cobas EGFR Mutation Test v2 is intended to identify a range of EGFR mutations in patients with non-small cell lung cancer, including T790M. The FDA approval of osimertinib is based on data from the two AURA Phase II studies (AURA extension and AURA2) which demonstrated efficacy in 411 EGFRm T790M NSCLC patients that had progressed on or after an EGFR TKI. In those trials, overall objective response rate (ORR) a measurement of tumour shrinkage) was 59% (95% CI: 54–64%). In a supportive Phase I study in 63 patients, ORR was 51% and median duration of response was 12.4 months.

Comment: The Medicines and Healthcare Products Regulatory Agency in the UK has awarded the drug Promising Innovative Medicine status as a treatment for locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC.

Comment: Competitor is CO 1686 (rociletinib) from Clovis Oncology which was filed at the EU in August 2015 and has a rolling submission at the FDA.