192TiP - NEPTUNE: A global, phase 3 study of durvalumab (MEDI4736) plus tremelimumab combination therapy versus standard of care (SoC) platinum-based chemot...

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 Tony S.K. Mok
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors T.S.K. Mok1, P. Schmid2, O. Arén3, O. Arrieta4, M. Gottfried5, A.R. Jazieh6, R. Ramlau7, K. Timcheva8, C. Martin9, S. McIntosh10
  • 1Department Of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, 22D Union Court - Shatin/HK
  • 2Centre For Experimental Cancer Medicine, Barts Cancer Institute - a Cancer Research UK Centre of Excellence, EC1M 6BQ - London/GB
  • 3Department Of Oncology, CIEC - Centro Internacional de Estudios Clínicos, Santiago/CL
  • 4Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City/MX
  • 5Department Of Oncology, Meir Medical Center, Kfar Saba/IL
  • 6Department Of Oncology, King Saud University for Health Sciences National Guards Health Affairs, Riyadh/SA
  • 7Department Of Oncology, Poznan University of Medical Sciences, Poznan/PL
  • 8Medical Oncology Clinic, MHAT for Women's Health, Sofia/BG
  • 9Department Of Clinical Oncology, Instituto Alexander Fleming, Buenos Aires/AR
  • 10Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield/GB

Abstract

Background

Current first-line therapy for advanced NSCLC is associated with poor survival and there remains a significant need for new, more effective treatments in this population. The blockade of immune checkpoints, such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), is a promising novel approach in cancer treatment. Based on preclinical data, targeting both checkpoints provides for non-redundant pathway blockade and potential synergy. Durvalumab (MEDI4736) is a selective, high affinity human IgG1 mAb that blocks programmed cell death ligand-1 (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. In a Phase 1b study (NCT02000947), durvalumab + tremelimumab has shown encouraging clinical activity (objective response rate [ORR] 28% [95% CI 15–45%] across tremelimumab 1 mg/kg cohorts [n = 39]) and manageable tolerability in pts with NSCLC regardless of PD-L1 status.

Trial design

NEPTUNE (NCT02542293) is a randomized, open-label, multicentre, global, Phase 3 study. Approximately 800 immunotherapy- and chemotherapy-naïve pts with advanced or metastatic (Stage IV) EGFR and ALK wild-type NSCLC (with either PD-L1+ or PD-L1 tumours) will be randomized (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); or SoC platinum-based doublet chemotherapy. Stratification factors are PD-L1 status, histology and smoking history. The primary endpoint is overall survival (OS). Secondary endpoints will assess progression-free survival (PFS), ORR, duration of response, and proportion of pts alive and progression free at 12 months using investigator assessments (RECIST v1.1); time from randomization to second progression; OS, PFS, and ORR in pts with PD-L1 NSCLC; safety (CTCAE v4.03) and tolerability; pharmacokinetics; and immunogenicity. Exploratory outcomes include potential biomarkers of response to treatment, and the impact of subsequent anticancer therapies on OS. Recruitment is ongoing.

Clinical trial identification

NCT02542293 (Release date 26 August 2015)

Legal entity responsible for the study

AstraZeneca PLC

Funding

AstraZeneca

Disclosure

T. Mok: SB/Ad B/honoraria: AZ, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Janssen, Clovis, GSK, NVS, BMS SB/honoraria: Amgen, Prime Ad B/honoraria: Merck, BioMarin, SFJ, ACEA, Vertex, Aveo & Biodesix, Ad B: geneDecode Stocks: Sanomics. R. Ramlau: Eli Lilly, Boehringer Ingelheim, MSD, Roche, Merck, KG&A. C. Martin: Advisory Board at Astra Zeneca, Boheringer Ingelheim, Roche Novartis. S. McIntosh: Contracted from Metis Medical Consultancy Limited to AstraZeneca to work on this study. All other authors have declared no conflicts of interest.