ASTRAZENECA REPORTS TOP-LINE RESULT OF TREMELIMUMAB MONOTHERAPY TRIAL IN
MESOTHELIOMA
Trial did not meet primary endpoint of improving overall survival in challenging
to treat mesothelioma patients with no currently approved treatment options in
the second-line setting
Tremelimumab remains key component of Immuno-Oncology combination strategy
across multiple tumour types
AstraZeneca and MedImmune, its global biologics research and development arm,
today announced that DETERMINE, the Phase IIb clinical trial of 10 mg/kg
tremelimumab monotherapy in second or third-line treatment of unresectable
malignant mesothelioma, did not meet its primary endpoint of overall survival.
Robert Iannone, Senior Vice President, Head of Immuno-Oncology, Global Medicines
Development at AstraZeneca, said: “We are disappointed that tremelimumab
monotherapy did not demonstrate a survival benefit in this patient population
with no approved medicines beyond first-line treatment. However, we remain
confident in tremelimumab’s clinical activity in combination, as shown in our
recently published Study 006 trial of tremelimumab and durvalumab in non-small
cell lung cancer.”
In addition to investigation as monotherapy for patients with mesothelioma,
tremelimumab is being studied in combination with AstraZeneca’s anti-PD-L1
investigational immunotherapy durvalumab in multiple tumour types, including non
-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck,
bladder, pancreatic, gastric and liver cancers. Preclinical data have suggested
that targeting both PD-L1 and CTLA-4 may have additive or synergistic effects.1
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antitumour activity in patients with locally advanced or metastatic NSCLC,
irrespective of PD-L1 status.2
The Company will complete a full evaluation of the final DETERMINE data, which
will be submitted for presentation at an upcoming medical meeting in 2016.
1Stewart et al. Preclinical modeling of immune checkpoint blockade (P2012). J
Immunol 2013: 190 (1 Meeting Abstracts): Abstract 214.7.
2Antonia S, et al. Safety and antitumour activity in a Phase 1b study of
combined checkpoint blockade with anti- PD-L1 (durvalumab) and anti-CTLA-4
(tremelimumab) in non-small cell lung cancer. The Lancet Oncology. Available at
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3Delgermaa V et al. Global mesothelioma deaths reported to the World Health
Organization between 1994 and 2008. Bull World Health Organ. 2011 Oct
1;89(10):716-24, 724A-724C
4Driscoll T et al. The global burden of disease due to occupational carcinogens.
Am J Ind Med. 2005 Dec;48(6):419-31.
About Mesothelioma
Mesothelioma is a rare and deadly form of cancer that affects the lining of the
lungs or abdomen. There is a high unmet medical need for mesothelioma
treatments, with median overall survival 9 to 12 months after initial
diagnosis.3 The disease causes approximately 43,000 deaths per year globally.4
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About the DETERMINE trial
DETERMINE (NCT01843374) is a randomised, double-blind, placebo-controlled Phase
IIb global trial with 571 patients across multiple countries. The trial
evaluated the safety and efficacy of tremelimumab versus placebo in the
treatment of unresectable pleural or peritoneal malignant mesothelioma.
About Tremelimumab
Tremelimumab is an investigational, selective human antibody directed against
cytotoxic T- lymphocyte-associated protein 4 (CTLA-4). By blocking the activity
of CTLA-4, tremelimumab “releases the brakes” on T cell activation and boosts
the immune response against cancer cells. Tremelimumab is being investigated in
an extensive clinical trial programme, as monotherapy or in combination with
durvalumab, in NSCLC, bladder, head and neck, gastric, pancreatic, HCC and blood
cancers. In 2015, the U.S. Food and Drug Administration granted tremelimumab
Fast Track Designation and Orphan Drug Designation as a potential treatment for
malignant mesothelioma, an aggressive, rare form of cancer that affects the
lining of the lungs and abdomen.
About Durvalumab
Durvalumab is an investigational human monoclonal antibody directed against
programmed death ligand-1 (PD-L1). PD-L1 expression enables tumours to evade
detection from the immune system through binding to PD-1 on cytotoxic T
lymphocytes. Durvalumab blocks PD-L1 interaction with both PD-1 and CD80 on T
cells, countering the tumour’s immune- evading tactics. Durvalumab is being
developed alongside other immunotherapies to activate the patient’s immune
system to attack the cancer. Durvalumab is being investigated in an extensive
clinical trial programme, as monotherapy or in combination with tremelimumab, in
NSCLC, bladder, head and neck, gastric, pancreatic, HCC and blood cancers. In
2015, durvalumab received Fast Track Designation for the treatment of patients
with PD-L1-positive metastatic SCCHN, and in 2016, durvalumab was granted
Breakthrough Designation by the U.S. Food and Drug Administration as a potential
treatment for metastatic urothelial bladder cancer.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing
portfolio of new medicines that has the potential to transform patients’ lives
and the Company’s future. With at least 6 new medicines to be launched between
2014 and 2020 and a broad pipeline of small molecules and biologics in
development, we are committed to advance New Oncology as one of AstraZeneca’s
six Growth Platforms focused on lung, ovarian, breast and blood cancers. In
addition to our core capabilities, we actively pursue innovative partnerships
and investments that accelerate the delivery of our strategy, as illustrated by
our investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms — immuno-oncology, the
genetic drivers of cancer and resistance, DNA damage repair and antibody drug
conjugates — and by championing the development of personalised combinations,
AstraZeneca has the vision to redefine cancer treatment and one day eliminate
cancer as a cause of death.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialisation of prescription
medicines, primarily for the treatment of diseases in three main therapy areas –
respiratory, inflammation, autoimmune disease (RIA), cardiovascular and
metabolic disease (CVMD) and oncology – as well as in infection and
neuroscience. AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more information
please visit: www.astrazeneca.com
CONTACTS
Media Enquiries
Neil Burrows UK/Global +44 20 7604 8032
Vanessa Rhodes UK/Global +44 20 7604 8037
Karen Birmingham UK/Global +44 20 7604 8120
Jacob Lund Sweden +46 8 553 260 20
Michele Meixell US +1 302 885 2677
Investor Enquiries
UK
Thomas Kudsk Larsen +44 7818 524185
Eugenia Litz RIA +44 7884 735627
Nick Stone CVMD +44 7717 618834
Craig Marks Finance +44 7881 615764
Christer Gruvris Consensus Forecasts +44 7827 836825
US
Lindsey Trickett Oncology, ING +1 240 543 7970
Mitch Chan Oncology +1 240 477 3771
Dial / Toll-Free +1 866 381 7277
Key: RIA – Respiratory, Inflammation and Autoimmunity, CVMD – Cardiovascular and
Metabolic Disease,
ING – Infection, Neuroscience and Gastrointestinal
29 February 2016
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