Data from the ongoing Phase 1 AURA study in patients with epidermal growth factor receptor mutation positive (EGFRm+), advanced non-small cell lung cancer (NSCLC), demonstrate that the overall disease control rate was 94% for patients with EGFR T790M+ tumors – meaning that their tumors shrank or became stable – following treatment with the investigational drug AZD9291.
The Phase 1 study, part of larger Phase 1/2 trial, is an ongoing, open label, dose escalation and expansion cohort study to investigate the safety and tolerability, pharmacokinetics, response to therapy and adverse events of AZD9291 in patients with advanced NSCLC who had disease progression following treatment with an EGFR tyrosine kinase inhibitor (TKI). The results were presented as an oral presentation during the official American Society of Clinical Oncology (ASCO) Annual Conference program.
Patients who have the EGFRm+ form of NSCLC, which occurs in 10-15% of NSCLC patients in Europe, 15% of NSCLC patients in the US and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently available EGFR TKIs, which block the cell signaling pathways that drive the growth of tumor cells. However, tumor cells almost always develop resistance to treatment, leading to disease progression. In more than half of patients with EGFRm+ NSCLC this resistance is caused by a secondary mutation known as T790M. There are currently no treatments approved for T790M mutation positive (T790M+) NSCLC.
Pasi Janne, director, Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, and Principal Investigator of the AURA study said: “As a treating oncologist, these results are promising for patients with EGFRm+ advanced NSCLC whose tumors have become resistant to treatment with established EGFR TKIs. Resistance to treatment is a major barrier to prolonged disease control. Treatments like AZD9291, which also target acquired resistance, could deliver important additional benefits to patients and redefine how we treat lung cancer.”
Results from the AURA study show that, amongst the 205 evaluable patients, the overall response rate (ORR) was 53% (unconfirmed + confirmed). The ORR was higher (64% confirmed and unconfirmed) in the 107 evaluable patients whose tumors were T790M+ compared to the 50 patients whose tumors were T790M- (22% confirmed and unconfirmed). In total, 94% (101/107) of patients whose tumors were T790M+ had their tumors shrink or become stable.
The most common AEs, reported in at least 10% of patients regardless of dose and mostly Grade 1 or 2, were: diarrhea, rash and nausea. Grade 3/4 AEs occurred in 24% of patients, with four patients (2%) requiring dose reductions and 10 (4%) patients discontinuing medication. Of the six interstitial lung disease (ILD)-like cases that have been reported, all patients have responded well to treatment and all cases are being investigated further.
The development program for AZD9291 includes AURA Phase 2 (the expansion portion of the current AURA Phase 1/2 study), AURA 2 (a separate Phase 2) and a Phase 3 study. The Phase 3 study in patients with T790M+ NSCLC is planned to commence later this year.
Susan Galbraith, SVP, head of Oncology iMED (AZ) said: “We are particularly excited about the potential that AZD9291 has demonstrated as there is a significant unmet need for effective treatments for lung cancer patients whose tumors have become resistant to their current therapy. These results formed the basis upon which the FDA recently granted AZD9291 Breakthrough Therapy Designation, which will help us expedite its development and potentially allow patient to gain access to this treatment faster. In addition to exploring the potential for this compound in different lines of treatment, we are also actively pursuing a range of AZD9291 combinations, both with immunotherapies and small molecule compounds.”
Date: June 3, 2014