1074TiP - Randomized, double-blind, placebo-controlled study of tremelimumab for second-line and third-line treatment of unresectable pleural or peritoneal m...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Mesothelioma
Cancer Immunology and Immunotherapy
Presenter Arnaud Scherpereel
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors A. Scherpereel1, R. Cornelissen2, A. Di Pietro3, H. Kindler4, K. Nackaerts5, S.J. Antonia6, L. Calabrò7, D. Fu8, P.B. Robbins9, R. Ibrahim10, M. Maio11
  • 1Service De Pneumologie Et D'oncologie Thoracique, Hôpital Albert Calmette, 59037 - Lille/FR
  • 2Department Of Pulmonary Medicine, Erasmus MC Cancer Institute, rotterdam/NL
  • 3Immuno-oncology, MedImmune, Gaithersburg/US
  • 4University Of Chicago, Division of Oncology, Chicago/US
  • 5Respiratory Oncology Unit, Univ Hospital Leuven, 3000 - Leuven/BE
  • 6Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, 33612 - Tampa/US
  • 7Department Of Oncology, Medical Oncology and Immunotherapy,University Hospital of Siena, Siena/IT
  • 8Medimmune, MedImmune, Gaithersburg/US
  • 9Oncology, MedImmune, 20878 - Gaithersburg/US
  • 10Immuno-oncology, AstraZeneca, 0000 - Gaithersburg/US
  • 11Division Of Medical Oncology And Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena/IT

Abstract

Background

Mesothelioma (MM) is a malignant tumor originating from the cells lining the coelomic cavities of the body, principally caused by asbestos exposure. Asbestos causes immunosuppression/dysfunction in the coelomic cavities micro-environment. First-line treatment for advanced MM is pemetrexed/platinum chemotherapy, but effective second-line treatments are lacking, highlighting a need for new treatment approaches. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a co-inhibitory receptor expressed on activated T cells. Tremelimumab is a human anti-CTLA-4 antibody that has been investigated in ∼1000 patients (pts) with various tumor types. A single institution, investigator-initiated phase 2 trial (NCT01649024) in advanced MM showed encouraging activity with tremelimumab, including disease control in 31% of 29 pts, two durable partial responses lasting 6 and 18 months (mos), median overall survival (OS) of 10.7 mos, and 1- and 2-year (y) survival rates of 48% and 37%, respectively (Calabrò, Lancet Oncol 2013).

Trial design

This is an ongoing global, multicenter, phase 2b, randomized, double-blind study (NCT01843374) in pts with unresectable pleural or peritoneal MM who progressed after 1–2 lines of treatment, including an anti-folate-platinum-based regimen for advanced disease. Pts, stratified by EORTC status (low vs. high risk), line of therapy (2nd vs. 3rd), and anatomical site (pleural vs. peritoneal), are randomized 2:1 to tremelimumab or placebo. The primary endpoint is OS. Secondary efficacy endpoints include OS rate at 18 mos, disease control rate (DCR), progression-free survival (PFS), overall response rate (ORR), and duration of response (based on modified RECIST criteria for pleural mesothelioma and modified RECIST criteria v1.1 for peritoneal mesothelioma), and patient-reported outcomes. Exploratory objectives include clinical outcomes based on immune-related response criteria; health-related quality of life, pain, disease-related symptoms, and health status in pts with durable clinical activity; and biomarkers. Recruitment is ongoing at ∼180 centers globally to a target of ∼564 randomized pts.This abstract was accepted and previously presented at the 2014 ASCO Annual Meeting Chicago, June 2014 (TPS7609).

Disclosure

A. Scherpereel: PI for the trial MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest; R. Cornelissen: MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest; A. Di Pietro: Employee of Medimmune and owns stock/stock options in AstraZeneca; H.L. Kindler: Research funding and ad hoc consultant MedImmune. MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest; K. Nackaerts: Research funding for conduct of MedImmune-sponsored ph IIb randomized placebo-controlled tremelimumab study for malignant mesothelioma patients(D4880C00003).MedImmune considers research funding received for the conduct of a MedImmune-sponsored study a COI; S.J. Antonia: Received honoraria from BMS & MedImmune/AZ for work related to designing, implementing, and analyzing various clinical trials. MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest; L. Calabrò: I have research funding to disclose from MedImmune. MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest; D. Fu: I am an employee of MedImmune, LLC, Gaithersburg. And I have stock of AstraZeneca; P.B. Robbins: I am an employee of MedImmune, LLC, Gaithersburg. I have stock of AstraZeneca; R. Ibrahim: I am an employee of MedImmune, LLC, Gaithersburg. And I have stock of AstraZeneca; M. Maio: Advisory Boards for BMS, GSK, Roche, MedImmune. He has received clinical research grants from BMS and MedImmune. MedImmune considers research funding received for the conduct of a MedImmune-sponsored study as COI.