A Phase 3, Randomised, Double-Blind, Placebo-Controlled, International Study of MEDI4736 in Patients with Locally Advanced, Unresectable NSCLC (Stage III) Who have not Progressed following Platinum-Based, Concurrent Chemoradiation Therapy (Pacific)

Abstract

ABSTRACT Background Thirty percent of patients with non-small cell lung cancer (NSCLC) present with Stage III disease. Concurrent chemoradiation therapy with curative intent is the treatment of choice for these patients. Despite treatment, progression-free survival (PFS) is usually short (approximately 9 months) and most patients ultimately die of metastatic disease. Chemotherapy and radiotherapy have been shown to up-regulate the expression of programmed cell-death ligand 1 (PD-L1), an important inhibitory checkpoint used by tumour cells to evade antitumour immune responses. MEDI4736 is a human IgG1 antibody that blocks PD-L1 binding to programmed cell-death 1 and CD80 and is engineered to prevent antibody dependent cell-mediated cytotoxicity. In a Phase 1 study, MEDI4736 has shown an encouraging safety profile and clinical activity in multiple tumour types, including NSCLC. Here we describe the PACIFIC study, which evaluates the efficacy and safety of MEDI4736 as sequential therapy in patients with locally advanced, unresectable NSCLC (Stage III) who have not progressed following definitive, platinum-based, concurrent chemoradiation therapy. Trial design In this phase 3, double-blind, international study (NCT02125461) patients will be randomised (2:1) to MEDI4736 (10 mg/kg intravenously every 2 weeks) or matching placebo for up to 12 months. Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy prior to randomisation. The primary objective is to assess the efficacy of MEDI4736 versus placebo in terms of overall survival and PFS (RECIST 1.1). Secondary outcome measures will assess efficacy (including proportion of patients alive at 24 months and objective response rate), safety and tolerability, pharmacokinetics, immunogenicity of MEDI4736 and its effect on symptoms and health-related quality of life. An independent data monitoring committee is in place to monitor safety. Recruitment is ongoing at sites across Australia, Asia, Europe, North and South America and South Africa. Disclosure S. Antonia: Consultant for MedImmune/AstraZeneca; A.D. Krebs, D. Jayawardene and P.K. Stockman: Employee of AstraZeneca and owns stock/stock options in AstraZeneca; M. Ballas: Employee of AstraZeneca and owns stock/stock options in AstraZeneca. Owns stock in Bristol Myers Squibb. All other authors have declared no conflicts of interest.