17TiPA PHASE 2, NON-COMPARATIVE, OPEN-LABEL, INTERNATIONAL STUDY OF MEDI4736 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC PD-L1-POSITIVE NSCLC (STAGE IIIB-IV) WHO HAVE RECEIVED ≥ 2 PRIOR SYSTEMIC TREATMENT REGIMENS (ATLANTIC)

ABSTRACT Background The inhibitory programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway plays a major role in controlling T cell activation and is utilised by tumour cells to evade antitumour responses. Anti-PD-L1 monoclonal antibodies (mAbs) have shown encouraging preclinical and clinical activity against a number of tumour types. MEDI4736 is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD-80 and is associated with a low frequency of anti-drug antibodies. Clinical activity for MEDI4736 in non-small cell lung cancer (NSCLC) has been observed in a Phase 1 study, with preliminary evidence indicating that PD-L1 expression is associated with a higher objective response. Here we describe an ongoing study to assess the efficacy and safety of MEDI4736 in patients with locally advanced or metastatic NSCLC. Trial design ATLANTIC (NCT02087423) is a phase 2, non-comparative, multicentre, international, open-label study, evaluating the efficacy and safety of MEDI4736 (10 mg/kg administered intravenously every 2 weeks for up to 12 months) in patients with PD-L1-positive locally advanced or metastatic NSCLC (Stage IIIb – IV). Eligible patients will have a WHO Performance Status of 0 or 1, and must have received at least 2 prior systemic treatment regimens, including a platinum-based chemotherapy regimen. Approximately 188 patients (∼50% known epidermal growth factor receptor [EGFR] or anaplastic lymphoma kinase [ALK] positive [Cohort 1] and ∼50% EGFR and ALK-negative [Cohort 2]), will be treated at ∼100 sites across North America, Asia, and Europe. Prior therapy for Cohort 1 patients must include the appropriate tyrosine kinase inhibitor. The primary outcome measure is objective response rate according to RECIST 1.1. Secondary outcome measures will further assess efficacy (including disease control rate, duration of response, deep sustained response, progression-free survival and overall survival), safety, tolerability, pharmacokinetics, and immunogenicity of MEDI4736. Recruitment is ongoing. This abstract was accepted and previously presented at ESMO 2014, Annals of Oncology, Volume 25, Supplement 4, 1335TiP. Disclosure N. Rizvi: I receive consulting income from MedImmune, Roche, Merck and BMS; M. Ballas: Employee of AstraZeneca and owns stock/stock options in AstraZeneca. Owns stock in Bristol Myers Squibb; D. Jayawardene and P.K. Stockman: Employee of AstraZeneca and owns stock/stock options in AstraZeneca; J.D. Powderly: Employment, Human Application Lab. Consultancy, BMS, Genentech, Amplimmune, Merck. Honoraria, BMS. Research funding, BMS, Genentech, Amplimmune, Merck, Astrazeneca, Imclone/Lilly. Speaker Bureau and Advisory Board BMS.