482TiP - Global, Phase 3 study of first-line durvalumab (MEDI4736) + tremelimumab vs standard of care platinum-based chemotherapy in advanced/metastatic NSC...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Non-Small-Cell Lung Cancer, Metastatic
Immunotherapy
Presenter Tony Mok
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors T. Mok1, P. Schmid2, G. de Castro, Jr3, K. Syrigos4, C. Martin5, N. Yamamoto6, O. Arén7, O. Arrieta8, M. Gottfried9, A.R. Jazieh10, R. Ramlau11, C. Timcheva12, L. Trani13
  • 1Department Of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, HK - Shatin/HK
  • 2Centre For Experimental Cancer Medicine, Barts Cancer Institute – A Cancer Research UK Centre of Excellence, Queen Mary University of London, London/GB
  • 3Faculdade De Medicina Da Usp, Instituto do Câncer do Estado de São Paulo, São Paulo/BR
  • 4Oncology Unit, 3rd Department Of Internal Medicine, National and Kapodistrian University of Athens, "Sotiria" General Hospital, Athens/GR
  • 5Department Of Clinical Oncology, Instituto Alexander Fleming, Buenos Aires/AR
  • 6Internal Medicine Iii (respiratory Medicine & Medical Oncology), Wakayama Medical University, Wakayama/JP
  • 7Department Of Oncology, CIEC Centro Internacional de Estudios Clínicos, Santiago/CL
  • 8Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City/MX
  • 9Department Of Oncology, Meir Medical Center, Kfar Saba/IL
  • 10Department Of Oncology, King Saud University for Health Sciences National Guards Health Affairs, Riyadh/SA
  • 11Department Of Oncology, Poznan University of Medical Sciences, Poznan/PL
  • 12Medical Oncology Clinic, MHAT for Women's Health, Sofia/BG
  • 13Global Medicines Development, AstraZeneca, Royston/GB

Abstract

Background

There is an urgent need for improved first-line therapy for advanced EGFR and ALK wild-type NSCLC, for which current molecularly targeted therapies are not indicated. Blockade of programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) immune checkpoints represents a promising anticancer therapeutic strategy. As PD-1 and CTLA-4 regulate immune responses by different mechanisms, targeting both pathways provides the potential for additive or synergistic effects. Durvalumab is a selective, high-affinity, engineered human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) binding to PD-1 and CD80. Tremelimumab is a selective human IgG2 mAb against CTLA-4. In a Phase 1b study (NCT02000947), durvalumab + tremelimumab demonstrated a manageable tolerability profile in advanced NSCLC, with clinical activity observed both in pts with high levels of tumour PD-L1 expression and in pts with low/no tumour PD-L1 expression.

Trial design

NEPTUNE (NCT02542293) is a randomised, open-label, multicentre, global, Phase 3 study assessing durvalumab + tremelimumab vs standard of care in immunotherapy- and chemotherapy-naïve pts with advanced/metastatic EGFR and ALK wild-type NSCLC. Pts with either PD-L1 high expression or PD-L1 low/no expression (≥25% or 

Clinical trial indentification

NCT02542293

Legal entity responsible for the study

AstraZeneca PLC

Funding

AstraZeneca

Disclosure

T. Mok: SB/Grants/Res/Stock/Hono/rEmploy: AZ Roche/Genentech, Pfizer EL BI MSD Amgen Janssen Clovis GSK Novartis BMS PrIME SFJ Roche MSD BioMarin ACEA Vertex BMS geneDecode OncoGenex Celgene Sanomics Merck Serono MSD GSK BMS Aveo & Biodesix CUHK. P. Schmid: Research: Roche, Genentech, AZ, Astellas, Medivation, Novartis, Oncogenex. G. de Castro, Jr: Speakers Bureau: AstraZeneca, MSD, BMS Consultant: Roche, MSD. K. Syrigos: Honoraria: BMS, Novartis, Roche, BI. C. Martin: Speakers Bureau: BMS, BI N. Yamamoto: Grants/Research Support: Chugai, BI, Ono Pharmaceutical CO Consultant: AZ, Chugai, BI, Ono Pharmaceutical CO Honoraria: AZ, Chugai, BI, MSD, Ono Pharmaceutical Co. O. Arén: Honoraria: BMS. R. Ramlau: Consultant: MSD, Roche, El Lilly, BI Honoraria: MSD, Roche, El Lilly, BI. L. Trani: Employee: AZ. All other authors have declared no conflicts of interest.