191TiP - MYSTIC: a global, phase 3 study of durvalumab (MEDI4736) plus tremelimumab combination therapy or durvalumab monotherapy versus platinum-based chem...

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Solange Peters
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors S. Peters1, S. Antonia2, S.B. Goldberg3, J.V. Heymach4, E.S. Kim5, K. Nakagawa6, V. Papadimitrakopoulou4, P. Mukhopadhyay7, S. McIntosh8, N.A. Rizvi9
  • 1Department Of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), 1011 - Lausanne/CH
  • 2Department Of Thoracic Oncology, H. Lee Moffitt Cancer Center, Tampa/US
  • 3Department Of Medicine, Yale University, Yale Cancer Center, New Haven/US
  • 4Department Of Thoracic/head And Neck Medical Oncology, MD Anderson Cancer Center, Houston/US
  • 5Department Of Solid Tumor Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte/US
  • 6Department Of Medical Oncology, Kinki University School of Medicine, 589-8511 - Osaka/JP
  • 7Global Medicines Development, Biometrics & Information Sciences, AstraZeneca, Gaithersburg/US
  • 8Global Medicines Development, AstraZeneca, Alderley Park, SK10 - Macclesfield/GB
  • 9Department Of Medicine, Columbia University Hospital, New York/US

Abstract

Background

Platinum-based doublets represent standard of care (SoC) first-line treatment for pts with advanced NSCLC. However, most pts do not achieve durable clinical benefit due to the rapid emergence of chemoresistance. Blockade of multiple immune checkpoints is being explored across different cancers. Dual blockade of the PD-1/PD-L1 and CTLA-4 pathways is the most promising immuno-oncology combination approach to date, and targeting both these pathways provides for non-redundant pathway blockade and synergy based on preclinical data. Durvalumab (MEDI4736) is a selective, high affinity human IgG1 mAb that blocks PD-L1 binding to PD-1 (IC50 0.1 nM) and CD80 (IC50 0.04 nM). Tremelimumab is a selective human IgG2 mAb inhibitor of CTLA-4. A comprehensive clinical development programme of durvalumab +/− tremelimumab in NSCLC is underway.

Trial design

MYSTIC (NCT02453282) is a randomised, open-label, multicentre, global, phase 3 study. 675 immunotherapy- and CT-naïve pts with advanced EGFR and ALK wild-type NSCLC will be randomised (1:1:1) to receive durvalumab (20 mg/kg i.v. every 4 weeks for up to 12 months) + tremelimumab (1 mg/kg i.v. every 4 weeks for up to 4 doses); durvalumab monotherapy (20 mg/kg i.v. every 4 weeks for up to 12 months); or SoC CT. Stratification factors are PD-L1 status and histology. The primary endpoint is progression-free survival (PFS). Secondary endpoints will further assess objective response rate, duration of response, proportion of pts alive and progression free at 12 months, time from randomisation to second progression, and overall survival; safety (CTCAE v4.03) and tolerability; health-related quality of life; pharmacokinetics; and immunogenicity. Exploratory outcomes include analysis of potential biomarkers of response to treatment, including comprehensive analysis of the tumour immune activation landscape by immunohistochemistry, as well as tumour mutation load, assessed on a tumour biopsy at trial entry. Recruitment is ongoing.

Clinical trial identification

NCT02453282 (Release date 20 May 2015)

Legal entity responsible for the study

AstraZeneca PLC

Funding

AstraZeneca

Disclosure

S. Peters: Consultancy, advisory board, lectures: F Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer, Boehrigner-Ingelheim, BMS, Daiichi-Sankyo, Morphotek, Merrimack, MSD, Merck Serono. S. Antonia: Advisory board: MedImmune, AstraZeneca. S.B. Goldberg: Grant: AstraZeneca, Boehringer Ingelheim Advisory Board: Clovis. J.V. Heymach: Research Grant: 1. AstraZeneca 2. GlaxoSmithKline 3. Bayer Consultant/Advisory Board: 1. Genentech 2. AstraZeneca 3. Novartis 4. GlaxoSmithKline 5. Lilly 6. Boerhinger Ingelheim 7. Synta 8. Exelixis. E.S. Kim: AstraZeneca consultancy and advisory role. K. Nakagawa: AstraZeneca K.K., Ono Pharmaceutical Co.,Ltd., Chugai Pharmaceutical Co.,Ltd., Bristol Myers Squibb Company for honoraria / Chugai Pharmaceutical Co.,Ltd., Ono Pharmaceutical Co.,Ltd., Bristol Myers Squibb Company MSD K.K. for research funding. V. Papadimitrakopoulou: Consulting or Advisory Role: Amgen Biothera Clovis Eli Lilly Genentech GlaxoSmithKline Janssen Merck Research Funding: Astellas AstraZeneca Bayer Bristol-Myers Squibb Celgene Clovis Oncology Janssen Merck Novartis Pfizer. P. Mukhopadhyay: Employee of AstraZenceca. Stock ownership AstraZeneca. S. McIntosh: Contracted from Metis Medical Consultancy Limited to AstraZeneca to work on this study. N.A. Rizvi: Personal fees from BMS, Roche, AstraZeneca, Merck and Novartis.