480TiP - Phase 3, randomised, open-label study of durvalumab (MEDI4736) in combination with tremelimumab versus platinum-based chemotherapy in first-line tr...

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 2
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Tony Mok
Citation Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532
Authors T. Mok1, P. Schmid2, O. Aren3, O. Arrieta4, M. Gottfried5, A.R. Jazieh6, R. Ramlau7, C. Timcheva8, C. Martin9, L. Zhao10, S. McIntosh11
  • 1Department Of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, 00 - Shatin/HK
  • 2Centre For Experimental Cancer Medicine, Barts Cancer Institute-Queen Mary University of London, London/GB
  • 3Oncology Department, CIEC - Centro Internacional de Estudios Clínicos, Santiago/CL
  • 4Subdirección De Investigación Clínica, Instituto Nacional de Cancerología (INCan), Mexico City/MX
  • 5Oncology Department, Meir Medical Center, Kfar Saba/IL
  • 6Oncology Department, 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
  • 10Gmd, Biometrics & Information Sciences, AstraZeneca, Gaithersburg/US
  • 11Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield/GB

Abstract

Background

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. As these pathways are non-redundant, dual targeting may have additive or synergistic antitumour activity. 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), and 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] 33% [95% CI 17–54%] across tremelimumab 1 mg/kg cohorts [n = 27]) and manageable tolerability in patients (pts) with both PD-L1-positive and -negative NSCLC. NEPTUNE is a Phase 3 study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy versus standard of care (SoC) platinum-based doublets in the first-line treatment of advanced or metastatic NSCLC.

Trial design

In this randomised, open-label, multicentre, global, Phase 3 study, approximately 800 immunotherapy- and chemotherapy-naïve pts with advanced or metastatic (Stage IV) NSCLC with no sensitising EGFR mutation nor ALK translocation will be randomised (1:1) to receive durvalumab (20 mg/kg IV every 4 weeks for up to 12 months) + tremelimumab (1 mg/kg IV every 4 weeks for up to 4 doses); or SoC 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 randomisation to second progression; OS, PFS, and ORR in pts with PD-L1-negative NSCLC; safety (CTCAE v4.03) and tolerability; PK; and immunogenicity. Exploratory outcomes include potential biomarkers of response to treatment, and the impact of subsequent anticancer therapies on OS. Study sites are being opened for recruitment.

Clinical trial identification

Disclosure

T. Mok: speaker, honoraria, shareholder, advisory board role: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Amgen, Janssen, Clovis Oncology, GSK, Novartis, BI, Sanomics Ltd., BioMarin, SFJ Pharmaceutical, ACEA Biosciences, Inc. P. Schmid: research funding from AstraZeneca (through my institution). O. Arén: Advisory Boards: BMS Chile, Novartis, Roche, Boehringer Ingelheim

C. Martin: Advisory boards: AstraZeneca, Elli Lilly, Roche. L. Zhao, S. McIntosh: employee of AstraZeneca and owns stock/stock options in AstraZeneca. All other authors have declared no conflicts of interest.