95TiP - A phase 3, randomised, double-blind, placebo-controlled, International study of MEDI4736 in patients with locally advanced, unresectable, stage 3 NS...

Date 17 April 2015
Event ELCC 2015
Session Poster lunch
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Cancer Immunology and Immunotherapy
Presenter Ben Creelan
Citation Annals of Oncology (2015) 26 (suppl_1): 24-28. 10.1093/annonc/mdv049
Authors B. Creelan1, N.O. Iannotti2, M.A. Salamat3, D. Jayawardene4, M. Ballas5, P.K. Stockman6, S.J. Antonia1
  • 1Department Of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, 33612 - Tampa/US
  • 2Hematology Oncology, Associates of the Treasure Coast, Port Saint Lucie/US
  • 3Hematology And Oncology, Cotton-O'Neil Clinical Research Center, Topeka/US
  • 4Biometrics & Information Sciences, Gmd, AstraZeneca, Gaithersburg/US
  • 5Immuno-oncology, Gmd, AstraZeneca, Gaithersburg/US
  • 6Immuno-oncology, Gmd, AstraZeneca, Macclesfield/UK

Abstract

Background

Standard treatment for locally advanced NSCLC has consisted of concurrent radiation with a platinum-based chemotherapy. Nonetheless, the majority of patients ultimately die due to cancer recurrence. Chemotherapy and radiotherapy upregulate the expression of programmed cell death ligand-1 (PD-L1), an inhibitory checkpoint that cancer cells harness to evade antitumour immune responses. MEDI4736 is a human IgG1 kappa mAb that blocks PD-L1 binding to its partner receptor; it is engineered to avoid antibody dependent cell-mediated cytotoxicity. MEDI4736 shows encouraging safety and efficacy in multiple tumour types, including NSCLC. Therefore, a clinical trial of MEDI4736 after completion of concurrent chemoradiation is scientifically justified, and may offer a high-impact advance in NSCLC treatment.

Trial design

This is a Phase 3, double-blind, international study (NCT02125461; PACIFIC). Patients will be randomised (2:1) to MEDI4736 (10 mg/kg IV every 2 weeks) or matching placebo for up to 12 months. Eligible subjects must have completed ≥2 cycles of platinum-based chemotherapy concurrent with definitive radiation therapy (≥60 Gy). Subjects are randomised within 14 days after radiation, and must have archival tissue available. Patients with metastatic disease or evidence of disease progression are excluded. Approximately 702 patients will be treated at over 310 sites across Australia, Asia, Europe, North and South America and South Africa. The primary endpoints are OS and PFS. PFS will be investigator-assessed, using RECIST v1.1. Secondary outcome measures will further assess efficacy of MEDI4736 (including duration of response, objective response rate, safety, pharmacokinetics, immunogenicity and health-related quality of life). Exploratory research will be conducted upon correlative biomarkers and healthcare resource utilisation. Interim analyses will be performed for PFS and OS. An independent data monitoring committee will monitor safety and efficacy in this trial. Recruitment is ongoing.

Clinical trial identification NCT02125461 (April 25, 2014)

Disclosure

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

S.J. Antonia: Received honoraria from BMS and MedImmune/Astra Zeneca for work related to designing, implementing, and analyzing various clinical trials.

All other authors have declared no conflicts of interest.