AURA3 Design: a Randomised, Phase III Study of Azd9291 Versus Second-Line Chemotherapy for Patients (PTS) with Egfr-Tki-Resistant (T790M) Advanced Non-Small Cell Lung Cancer

Abstract

Background: EGFR‐TKIs are first‐line therapy for pts with advanced non‐small cell lung cancer (aNSCLC) harbouring an EGFR‐TKI‐sensitising mutation (EGFRm). Most pts treated with an EGFR‐TKI develop resistance and in 60% of cases this is due to an EGFR exon 20 T790M mutation. AZD9291 is an oral, irreversible EGFR‐TKI selective for both EGFRm and resistance EGFR T790M mutations. AZD9291 has shown clinical activity in a Phase I/II study of pts with EGFRm/T790M aNSCLC whose disease has progressed during prior EGFR‐TKI therapy. Trial design: AURA3 (NCT02151981) is a global, multicentre, Phase III, open‐label study comparing the efficacy of AZD9291 with platinum‐based chemotherapy (CT) as second‐line therapy in pts with progressing advanced/metastatic T790M positive NSCLC, with documented EGFRm, who have received prior EGFR‐TKI therapy. The study will recruit approximately 610 CT‐naïve pts, male and female, 18 years and over (20 years and over in Japan). Pts must have shown disease progression on an approved first‐line EGFR‐TKI; biopsy on progression will be centrally tested and pts with T790M positive NSCLC will be recruited. An estimated 1540 pts will be screened. Pts will be randomised 2:1 to receive AZD9291 (80 mg qd, orally) or platinum‐based doublet CT (pemetrexed 500 mg/m2 + carboplatin AUC5 or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2; up to 6 cycles) in accordance with institutional guidelines on Day 1 of every 21‐day cycle. The primary objective is to compare the efficacy of AZD9291 versus CT with the primary endpoint of progression‐free survival (PFS) assessed according to RECIST v1.1. Secondary objectives include: objective response rate, duration of response, disease control rate, overall survival and the safety and tolerability profile of AZD9291 compared with CT.