Blueprint
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of August
2019
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Update
on the Phase III NEPTUNE trial
21 August 2019 07:00 BST
Update on the Phase III NEPTUNE trial
of Imfinzi plus
tremelimumab in Stage IV non-small cell lung cancer
AstraZeneca today announced final overall survival (OS) results
from the Phase III NEPTUNE trial, a randomised, open-label,
multi-centre, global trial of Imfinzi (durvalumab) in combination with
tremelimumab, an anti-CTLA4 antibody, vs. standard-of-care (SoC)
platinum-based chemotherapy in previously-untreated Stage IV
(metastatic) non-small cell lung cancer (NSCLC) patients. The trial
was performed in an all-comers population, and the primary analysis
population was patients with a high tumour mutational burden (TMB).
TMB is a measurement of the number of mutations within the genome
(DNA) of a tumour, and tumours with high levels of TMB may be more
visible to the immune system.1,2
In the primary analysis population of patients whose blood TMB was
20 or more mutations per megabase (mut/Mb), the combination
of Imfinzi and tremelimumab did not meet the primary
endpoint of improving OS compared to SoC chemotherapy. The safety
and tolerability profile for the combination
of Imfinzi and tremelimumab was consistent with
previous trials.
José Baselga, Executive Vice President, Oncology R&D said:
"We are fully committed to a deep analysis of the vast clinical and
biomarker data from this trial to gain further insights to improve
Immuno-Oncology approaches for patients with metastatic non-small
cell lung cancer."
AstraZeneca will submit the full results for presentation at a
forthcoming medical meeting.
Imfinzi is also being
tested as monotherapy in the Phase III PEARL trial, and in
combination with chemotherapy with or without tremelimumab in the
Phase III POSEIDON trial as part of an extensive late-stage
Immuno-Oncology programme in Stage IV NSCLC.
About NEPTUNE
The NEPTUNE trial is a randomised, open-label, multi-centre,
global, Phase III trial of Imfinzi in combination with tremelimumab vs.
SoC platinum-based chemotherapy in the 1st-line treatment
of patients with Stage IV (metastatic) NSCLC. The trial
population included patients with non-squamous or squamous
histologies, no epidermal growth factor receptor (EGFR) or
anaplastic lymphoma kinase (ALK) mutation and the full range of
PD-L1 expression levels. The primary endpoint was OS in
patients with high blood TMB defined as ≥ 20
mut/Mb.
The trial is being conducted in more than 200 centres across 29
countries, including the US, Europe, South and Central America, the
Middle East and Asia.
About Stage IV NSCLC
Lung cancer is the leading cause of cancer death among both men and
women and accounts for about one-fifth of all cancer
deaths.3 Lung
cancer is broadly split into NSCLC and SCLC, with 80-85% classified
as NSCLC.4 Stage
IV is the most advanced form of lung cancer and is often referred
to as metastatic disease.5Lung
cancer patients are most commonly diagnosed after the tumour has
spread outside of the lung.6 For
these patients with metastatic disease, prognosis is particularly
poor, as only 1 in 10 will be alive five years after
diagnosis.7
About Imfinzi
Imfinzi (durvalumab) is a
human monoclonal antibody that binds to PD-L1 and blocks the
interaction of PD-L1 with PD-1 and CD80, countering the tumour's
immune-evading tactics and releasing the inhibition of immune
responses.
Imfinzi is approved for
unresectable, Stage III NSCLC in 49 countries including the US,
Japan, and across the EU, based on the Phase III PACIFIC
trial. Imfinzi is also approved for previously-treated
patients with advanced bladder cancer in the US, Canada, Brazil,
Australia, Israel, India, United Arab Emirates, Qatar, Macau and
Hong Kong.
As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in
combination with tremelimumab, an anti-CTLA4 monoclonal antibody
and potential new medicine, as a treatment for patients with NSCLC,
small-cell lung cancer (SCLC), bladder cancer, head and neck
cancer, liver cancer, cervical cancer, biliary tract cancer and
other solid tumours.
About tremelimumab
Tremelimumab is a human monoclonal antibody and potential new
medicine that targets the activity of cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the
activity of CTLA-4, contributing to T cell activation and boosting
the immune response to cancer. Tremelimumab is being tested in a
clinical trial programme in combination
with Imfinzi in NSCLC, bladder cancer, head and neck
cancer, liver cancer and blood cancers.
About AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential
new medicines in late-stage clinical development for the treatment
of different forms of lung cancer spanning several stages of
disease, lines of therapy and modes of action. We aim to address
the unmet needs of patients with EGFR-mutated tumours as a genetic
driver of disease, which occur in 10-15% of NSCLC patients in the
US and EU and 30-40% of NSCLC patients in Asia, with our approved
medicines Iressa (gefitinib) and Tagrisso (osimertinib), and ongoing Phase III trials
ADAURA, LAURA, FLAURA and FLAURA2 as well as the Phase II
combination trials SAVANNAH and ORCHARD.8-10
Our extensive late-stage Immuno-Oncology programme focuses on lung
cancer patients without a targetable genetic mutation which
represents approximately three-quarters of all patients with lung
cancer.11 Imfinzi (durvalumab),
an anti-PDL1 antibody, is in development for patients with advanced
disease (Phase III trials NEPTUNE, POSEIDON, PEARL, and CASPIAN)
and for patients in earlier stages of disease including
potentially-curative settings (Phase III trials AEGEAN, PACIFIC-2,
ADRIATIC, ADJUVANT BR.31, PACIFIC-4, and PACIFIC-5) both as
monotherapy and in combination with tremelimumab and/or
chemotherapy.
About AstraZeneca's approach to Immuno-Oncology (IO)
IO is a therapeutic approach designed to stimulate the body's
immune system to attack tumours. Our IO portfolio is anchored by
immunotherapies that have been designed to overcome anti-tumour
immune suppression. We believe that IO-based therapies offer the
potential for life-changing cancer treatments for the clear
majority of patients.
We are pursuing a comprehensive clinical-trial programme that
includes Imfinzi (anti-PDL1) as monotherapy and in
combination with tremelimumab (anti-CTLA4) in multiple tumour
types, stages of disease, and lines of therapy, using the PD-L1
biomarker as a decision-making tool to define the best potential
treatment path for a patient. In addition, the ability to combine
our IO portfolio with radiation, chemotherapy, small targeted
molecules from across our Oncology pipeline, and from our research
partners, may provide new treatment options across a broad range of
tumours.
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 six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, the
Company is committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
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, science-led biopharmaceutical company that
focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, CVRM and Respiratory. AstraZeneca
operates in over 100 countries and its innovative medicines are
used by millions of patients worldwide. For more information,
please visit astrazeneca.com and
follow us on Twitter @AstraZeneca.
Media Relations
|
|
|
|
Gonzalo
Viña
|
|
+44 203 749 5916
|
|
Rob
Skelding
|
Oncology
|
+44 203 749 5821
|
|
Rebecca
Einhorn
|
Oncology
|
+1 301 518 4122
|
|
Matt
Kent
|
BioPharmaceuticals
|
+44 203 749 5906
|
|
Jennifer
Hursit
|
Other
|
+44 203 749 5762
|
|
Christina
Malmberg Hägerstrand
|
Sweden
|
+46 8 552 53 106
|
|
Michele
Meixell
|
US
|
+1 302 885 2677
|
|
|
|
|
|
Investor Relations
|
|
|
|
Thomas
Kudsk Larsen
|
|
+44 203 749 5712
|
|
Henry
Wheeler
|
Oncology
|
+44 203 749 5797
|
|
Christer
Gruvris
|
BioPharmaceuticals (cardiovascular, metabolism)
|
+44 203 749 5711
|
|
Nick
Stone
|
BioPharmaceuticals (respiratory, renal)
|
+44 203 749 5716
|
|
Josie
Afolabi
|
Other medicines
|
+44 203 749 5631
|
|
Craig
Marks
|
Finance, fixed income
|
+44 7881 615 764
|
|
Jennifer
Kretzmann
|
Corporate access, retail investors
|
+44 203 749 5824
|
|
US
toll-free
|
|
+1 866 381 72 77
|
|
Adrian Kemp
Company Secretary
AstraZeneca PLC
References
1. ESMO. "Tumour Mutational Load: ESMO Biomarker Factsheet."
Available at: http://oncologypro.esmo.org/Education-Library/Factsheets-on-Biomarkers/Tumour-Mutational-Load Date
Accessed: August 2019.
2. Huang A, et al. T-cell invigoration to tumour burden ratio
associated with anti-PD-1 response. Nature. 2017;454:60-65.
3. World Health Organization. International Agency for Research on
Cancer. Available athttp://globocan.iarc.fr/Pages/fact_sheets_population.aspx.
Accessed August 2019.
4. LUNGevity Foundation. Types of Lung Cancer. Available
at https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed August 2019.
5. Cancer.Net. Lung Cancer - Non-Small Cell: Stages. Available
at https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/stages.
Accessed August 2019.
6. Ridge C, et al. Epidemiology of Lung
Cancer. Semin Intervent
Radiol.
2013;30:93-98.
7. Cancer.Net. Lung Cancer - Non-Small Cell -
Statistics." Available at www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics.
Accessed August 2019.
8. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and
Histological Samples in Non-Small Cell Lung Cancer: a Polish,
Single Institution Study and Systematic Review of European
Incidence. Int J Clin Exp
Pathol.
2013:6;2800-12.
9. Keedy VL, et al. American Society of Clinical Oncology
Provisional Clinical Opinion: Epidermal Growth Factor Receptor
(EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell
Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor
Therapy. J Clin
Oncol.
2011:29;2121-27.
10. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a
Review of Available Methods and Their Use for Analysis of Tumour
Tissue and Cytology Samples. J Clin
Pathol.
2013:66;79-89.
11. Pakkala, S, et al. Personalized therapy for lung cancer:
striking a moving target. JCI Insight. 2018;3(15):e120858.
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
21 August 2019
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|