Osimertinib is an oral, potent, CNS active, irreversible EGFR-TKI selective for EGFR-TKI sensitising and T790M resistance mutations. AURA17 (NCT02442349) is a Phase II, open-label, single arm study investigating the safety and efficacy of osimertinib in Asia-Pacific pts with T790M-positive advanced NSCLC, who had progressed on prior EGFR-TKI therapy, with or without additional anti-cancer regimens.
Eligible pts had measureable disease, WHO performance status 0/1 and acceptable organ function; asymptomatic CNS metastases were allowed. T790M-positive status was confirmed by central testing of biopsy samples using the cobas® EGFR Mutation Test. Osimertinib 80 mg was administered orally once daily until disease progression. The primary endpoint was objective response rate (ORR) according to RECIST 1.1 by blinded independent central review. Secondary endpoints included duration of response (DoR), PFS, disease control rate (DCR), overall survival, safety and tolerability.
As of 4 Nov 2016 data cut-off (DCO), 171 pts had received osimertinib (53 [31%] second-line; 118 [69%] ≥third-line), median treatment exposure was 12.3 (range 0.2–14.6) mo. Median age 60 (range 26–82) years; female 68%; Chinese ethnicity 87%; never smokers 78%; EGFR Exon 19 deletion 64%; EGFR L858R mutation 35%; CNS metastases at study entry 37%. Confirmed ORR in pts evaluable for response (n = 166) was 63% (95% confidence interval [CI] 55, 70) and DCR was 89% (95% CI 83, 93). Median DoR was 9.9 mo (95% CI 8.3, not calculable). Median PFS in the full analysis set (n = 171) was 9.7 mo (95% CI 7.0, 11.1); 94 pts (55%) had progression. At DCO, 39 pts had died (23%). All causality adverse events (AEs) of CTCAE Grade ≥3 were reported by 43 (25%) pts. Most common AEs were diarrhoea 35% (Grade ≥3 1%) and rash grouped term 27% (Grade ≥3 0%). There was one reported case of interstitial lung disease and pneumonitis, respectively.
The high ORR of 63% was supported by the durable response assessed by DoR (median 9.9 mo) and PFS (median 9.7 mo). The efficacy data were consistent with global clinical trials of osimertinib. No new safety signals were observed.
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Legal entity responsible for the study
C. Zhou: Lecture honorarium: Eli Lily, AZ, Roche, Pfizer, Sanofi, BI, Henrui AB: Roche, BI, AZ. Y. Chen: AstraZeneca employee. X. Huang: I am an employee of AstraZeneca. M. Cantarini: Employee and shareholder of AstraZeneca. Y-L. Wu: Speaker fees from AstraZeneca, Roche, Eli Lilly, Sanofi, Pfizer. All other authors have declared no conflicts of interest.