449PD - Updated Safety and Efficacy from a Phase I Study of Azd9291 in Patients (Pts) with Egfr-Tki-Resistant Non-Small Cell Lung Cancer (Nsclc)

Abstract

ABSTRACT Aim: AZD9291 is a potent, selective, irreversible EGFR-TKI, effective against the EGFR-TKI-sensitising (EGFRm+) and resistance T790M mutations. Here we report updated data from the ongoing Phase I study of AZD9291 in pts with EGFRm+ NSCLC (AURA; NCT01802632). Methods: Pts with EGFRm+ NSCLC and acquired resistance to EGFR-TKIs were enrolled in a multicentre trial into dose escalation and expansion cohorts. AZD9291 was administered orally, at doses of 20–240 mg once daily. Stable brain metastases were allowed. Primary objective was safety and tolerability; anti-tumour activity was a secondary objective. Prospective mandatory central T790M testing was required in the expansion cohorts and was optional for dose escalation cohorts. Results: As of 2 April 2014, 232 pts (female 63%, median age 60, Asian/Caucasian 64%/34%, immediate prior EGFR-TKI therapy 60%) were enrolled: 31 pts in the dose escalation and 201 pts in the dose expansion cohorts, of whom 120 were T790M+ by central tumour testing. Adverse events (AEs) were mostly mild (CTCAE Grade 1/2), with diarrhoea (39%), rash (36%) and nausea (18%) the most commonly reported. 8 pts (3%) had dose reductions. Grade ≥3 AEs occurred in 24% of pts. There were 8 ILD-like reports. At the recommended Phase II dose of 80 mg QD, rash and diarrhoea occurred in 27% (Grade 3, 0%) and 20% (Grade 3, 1%) of pts, respectively. Among all evaluable pts to date, RECIST responses were observed at all dose levels. The confirmed overall response rate (ORR) in patients with centrally tested EGFR T790M+ tumours was 56% (56/100; 95% CI 46, 66%) and in patients with EGFR T790M- tumours the confirmed ORR was 17% (8/48; 95% CI 8, 30%). In 56 pts with EGFR T790M+ tumours and confirmed response: longest duration of response to date was ongoing at approx 7.5 months; 7/56 pts responded for at least >6 months and 46/56 have an ongoing response Conclusions: AZD9291 has been well tolerated at all dose levels tested. Clinical activity has been shown in pts with centrally confirmed EGFR T790M+ NSCLC, with durable responses of >6 months. Disclosure: J.C. Yang: Advisory board: Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Roche/Genentech, AstraZeneca, Merck, Bayer, Clovis Oncology. Corporate-sponsored research: Boehringer Ingelheim; D. Planchard: Advisory boards: AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, Roche, BMS S.S. Ramalingam: Advisory boards: AstraZeneca, Boehringer Ingelheim, Genentech; L. Horn: Research funding: Astellas. Compensated advisory boards: Bristol-Myers Squibb, Clovis, Helix Bio. Uncompensated advisory boards: PUMA, Xcovery. Steering Committee (uncompensated): Bayer. Honoraria: Boehringer Ingelheim; E. Felip: Advisory boards: Boehringer Ingelheim, Novartis, Roche, BMS, Lilly; P. Frewer, M. Cantarini and S. Ghiorghiu: Employment and stock ownership: AstraZeneca; M. Ranson: Advisory boards: AstraZeneca; P.A. Janne: Consultant or advisory role: AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Pfizer, Merrimack Pharmaceuticals, Chugai, Immunogen. Stock ownership: Gatekeeper. Other: Lab Corp. All other authors have declared no conflicts of interest.