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 February 2021
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.
Lynparza: IDMC recommend early analysis of OlympiA
17 February 2021 07:00 GMT
IDMC has concluded that OlympiA trial
of Lynparza crossed superiority boundary for
invasive disease-free survival vs. placebo at planned interim
analysis
OlympiA Phase III trial of Lynparza in the adjuvant treatment of
BRCA-mutated high-risk HER2-negative early breast cancer will be
analysed and reported early
The OlympiA Phase III trial for AstraZeneca and
MSD's Lynparza will move to early primary analysis and
reporting following a recommendation from the Independent Data
Monitoring Committee (IDMC).
Based on the planned interim analysis, the IDMC concluded that the
trial crossed the superiority boundary for its primary endpoint of
invasive disease-free survival (iDFS) and demonstrated a
sustainable, clinically relevant treatment effect
for Lynparza versus placebo for patients with germline
BRCA-mutated (gBRCAm) high-risk human epidermal growth
factor receptor 2 (HER2)-negative early breast cancer, and recommend
primary analysis now take place.
The OlympiA Phase III trial is a partnership between Breast
International Group (BIG), NRG Oncology, the US National Cancer
Institute (NCI), Frontier Science & Technology Research
Foundation (FSTRF), AstraZeneca and MSD.1 The
trial is sponsored by NRG Oncology in the US and by AstraZeneca
outside the US.
An estimated 2.3 million women were diagnosed with breast cancer
worldwide in 2020, and BRCA mutations are found in approximately 5%
of breast cancer patients.2-10 Around
55-65% of women with a BRCA1 mutation and approximately 45% with a
BRCA2 mutation will develop breast cancer before the age of
70.11
Andrew Tutt, Global Chair of the OlympiA Phase III trial and
Professor, Institute of Cancer Research and Kings College London,
said: "We are delighted that our global academic and industry
partnership has been able to help investigate a possible
personalised treatment for women with hereditary breast
cancer. The most common cause of hereditary breast cancer is
an inherited mutation in the BRCA1 or BRCA2 genes which also may cause the disease to
develop at a significantly earlier age than is usual.
The OlympiA trial has allowed us to go beyond using genetic
testing to identify patients who are at risk of this disease and
explore the potential of Lynparza to prevent disease recurrence for these
patients. We look forward to analysing and presenting the full
results of the trial at a forthcoming medical
meeting."
José Baselga, Executive Vice President, Oncology R&D,
said: "Breast cancer remains one of the most common cancers
globally and despite advances in treatment, many patients with
high-risk disease will unfortunately develop a recurrence. We look
forward to reviewing the results."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: " Analysis of the OlympiA trial, based upon the IDMC
recommendation, could represent a potential step forward for
patients with early-stage, high-risk primary breast cancer with a
germline BRCA mutation."
In its communication, the IDMC did not raise any new safety
concerns. The trial will continue to assess the key secondary
endpoints of overall survival and distant disease-free
survival.
Early breast cancer
Breast cancer is the most common cancer among women worldwide and
an estimated 90% of all breast cancer is diagnosed at an early
stage.12,13 Breast
cancer is one of the most biologically diverse tumour types with
various factors fuelling its development and
progression.14 The
discovery of biomarkers in the development of breast
cancer has greatly impacted scientific understanding of the
disease.15
BRCA1 and BRCA2
BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are
human genes that produce proteins responsible for repairing damaged
DNA and play an important role maintaining the genetic stability of
cells. When either of these genes is mutated or altered such that
its protein product either is not made or does not function
correctly, DNA damage may not be repaired properly, and cells
become unstable. As a result, cells are more likely to develop
additional genetic alterations that can lead to
cancer and confer sensitivity
to PARP inhibitors including Lynparza.16-19
OlympiA
OlympiA is a Phase III, double-blind, parallel group,
placebo-controlled, multicentre trial testing the efficacy and
safety of Lynparza tablets versus placebo as adjuvant treatment
in patients with gBRCAm high-risk HER2-negative early breast
cancer, who have completed definitive local treatment and
neoadjuvant or adjuvant chemotherapy. The primary endpoint of the
trial is iDFS defined as time from randomisation to date of first
treatment failure that is loco-regional or distant recurrence or
new cancer or death from any cause.1
NRG Oncology
NRG Oncology is a network group funded by the NCI, a part of the
National Institutes of Health. All of the NCI funded network groups
participated in the trial. The NCI and AstraZeneca are
collaborating under a Cooperative Research and Development
Agreement.
NRG Oncology brings together the National Surgical Adjuvant Breast
and Bowel Project, the Radiation Therapy Oncology Group, and the
Gynaecologic Oncology Group, with the mission to improve the lives
of cancer patients by conducting practice-changing
multi-institutional clinical and translational
research.
BIG
The Breast International Group (BIG) is an international
not-for-profit organisation for academic breast cancer research
groups from around the world, based in Brussels,
Belgium.
Founded by leading European opinions leaders in 1999, the
organisation aims to address fragmentation in European breast
cancer research and now represents a network of over 55 like-minded
research groups affiliated with specialised hospitals, research
centres and leading experts across approximately 70 countries on
six continents.
BIG's research is supported in part by its philanthropy unit, known
as BIG
against breast cancer, which is
used to interact with the general public and donors, and to raise
funds for BIG's purely academic breast cancer trials and research
programmes.
FSTRF
Frontier Science & Technology Research Foundation (FSTRF) is a
non-profit, research organisation which supports research networks,
pharmaceutical companies and investigators to conduct scientifically meaningful high-quality
clinical trials. The OlympiA trial
involved research staff in the US and in the Affiliate office in
Scotland.
FSTRF works with
scientists and technicians in more than 800 laboratories,
universities and medical centres around the world to provide a
comprehensive range of research services throughout the clinical
trial process including design, analysis and
reporting.
Through its work, FSTRF aims to advance the application of
statistical science and practice and data management techniques in
science, healthcare and education.
Lynparza
Lynparza (olaparib) is a
first-in-class PARP inhibitor and the first targeted treatment to
block DNA damage response (DDR) in cells/tumours harbouring a
deficiency in homologous recombination repair (HRR), such as
mutations in BRCA1 and/or BRCA2. Inhibition of PARP
with Lynparza leads to the trapping of PARP bound to DNA
single-strand breaks, stalling of replication forks, their collapse
and the generation of DNA double-strand breaks and cancer cell
death. Lynparza is being tested in a range of PARP-dependent
tumour types with defects and dependencies in the DDR
pathway.
Lynparza is currently
approved in a number of countries, including those in the EU, for
the maintenance treatment of platinum-sensitive relapsed ovarian
cancer. It is approved in the US, the EU, Japan, China, and several
other countries as 1st-line maintenance treatment of BRCA-mutated
advanced ovarian cancer following response to platinum-based
chemotherapy. It is also approved in the US, EU and Japan as a
1st-line maintenance treatment with bevacizumab for patients with
homologous recombination deficient (HRD)-positive advanced ovarian
cancer (BRCAm and/or genomic instability). Lynparza is approved in the US, Japan, and a number
of other countries for germline BRCA-mutated, HER2-negative,
metastatic breast cancer, previously treated with chemotherapy; in
the EU, this includes locally advanced breast cancer. It is also
approved in the US, the EU, Japan and several other countries for
the treatment of gBRCAm metastatic pancreatic
cancer. Lynparza is approved in the US for HRR gene-mutated
metastatic castration-resistant prostate cancer (BRCAm and other
HRR gene mutations) and in the EU and Japan for BRCAm metastatic
castration-resistant prostate cancer. Regulatory reviews are
underway in several countries for ovarian, breast, pancreatic and
prostate cancers.
Lynparza, which is being
jointly developed and commercialised by AstraZeneca and MSD, has
been used to treat over 40,000 patients
worldwide. Lynparza has the broadest and most advanced clinical
trial development programme of any PARP inhibitor, and AstraZeneca
and MSD are working together to understand how it may affect
multiple PARP-dependent tumours as a monotherapy and in combination
across multiple cancer types. Lynparza is the foundation of AstraZeneca's
industry-leading portfolio of potential new medicines targeting DDR
mechanisms in cancer cells.
The AstraZeneca and MSD strategic oncology
collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth,
NJ, US, known as MSD outside the US and Canada, announced a global
strategic oncology collaboration to co-develop and
co-commercialise Lynparza,
the world's first PARP inhibitor, and Koselugo (selumetinib),
a mitogen-activated protein kinase (MEK) inhibitor, for
multiple cancer types. Working together, the companies will
develop Lynparza and Koselugo in
combination with other potential new medicines and as
monotherapies. Independently, the companies will
develop Lynparza and Koselugo in
combination with their respective PD-L1 and PD-1
medicines.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology,
AstraZeneca is starting to challenge, and redefine, the current
clinical paradigm for how breast cancer is classified and treated
to deliver even more effective treatments to patients in need -
with the bold ambition to one day eliminate breast cancer as a
cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising
compounds in development that leverage different mechanisms of
action to address the biologically diverse breast cancer tumour
environment. AstraZeneca aims to continue to transform outcomes for
HR-positive breast cancer with foundational
medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation
selective estrogen receptor degrader (SERD) and potential new
medicine camizestrant (AZD9833). PARP
inhibitor, Lynparza is a targeted treatment option for
metastatic breast cancer patients with an inherited BRCA mutation.
AstraZeneca with MSD continue to research Lynparza in metastatic breast cancer patients with an
inherited BRCA mutation and are exploring new opportunities to
treat these patients earlier in their disease
state.
Building on the first approval of Enhertu (trastuzumab deruxtecan), a HER2-directed
antibody-drug conjugate (ADC), in previously treated HER2-positive
metastatic breast cancer, AstraZeneca and Daiichi Sankyo are
exploring its potential in earlier lines of treatment and in new
breast cancer settings. To bring much needed treatment options to
patients with triple-negative breast cancer, an aggressive form of
breast cancer, AstraZeneca is testing
immunotherapy Imfinzi (durvalumab) in combination with other
oncology medicines, including Lynparza and Enhertu, assessing the potential of AKT kinase inhibitor,
capivasertib, in combination with chemotherapy, and collaborating
with Daiichi Sankyo to explore the potential of TROP2-directed ADC,
datopotamab deruxtecan.
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 seven new medicines 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.
By harnessing the power of six scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage
Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies
- 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.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) 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, Cardiovascular, Renal & Metabolism, and Respiratory
& Immunology. Based in Cambridge, UK, AstraZeneca operates in
over 100 countries and its innovative medicines are used by
millions of patients worldwide. Please
visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. ClinicalTrials.gov. Olaparib as Adjuvant Treatment in Patients
with Germline BRCA Mutated High Risk HER2 Negative Primary Breast
Cancer (OlympiA). Available at https://clinicaltrials.gov/ct2/show/NCT02032823. Accessed
February 2021.
2. GLOBOCAN. Breast Cancer. Available at https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf. Accessed
February 2021.
3. Gomes M.C, et al. Prevalence of BRCA1 and BRCA2 Mutations in
Breast Cancer Patients from Brazil. Breast Cancer Res
Treat. 2007
Jul;103(3):349-53.
4. Hernandez J.E, et al. Prevalence of BRCA1 and BRCA2 Mutations in
Unselected Breast Cancer Patients from Medellín,
Colombia. Hered Cancer in Clin
Pract. 2014;12:11.
5. Bu R, et al. Identification of Novel BRCA Founder Mutations
in Middle Eastern Breast Cancer Patients Using Capture and Sanger
Sequencing Analysis. Int J
Cancer.
2016;139:1091-1097.
6. Abugattas J, et al. Prevalence of BRCA1 and BRCA2 Mutations in
Unselected Breast Cancer Patients From
Peru. Clin Genet. 2015 October;88(4):371-375.
7. Kast K, et al. Prevalence of BRCA1/2 Germline Mutations in
21,401 Families with Breast and Ovarian Cancer. J Med
Genet.
2016;53:465-471.
8. Winter C, et al. Targeted Sequencing of BRCA1 and BRCA2 Across a
Large Unselected Breast Cancer Cohort Suggests That One-third of
Mutations Are Somatic. Ann Oncol. 2016;27:1532-1538.
9. Hoberg-Vetti H, et al. BRCA1/2 Testing in Newly Diagnosed Breast
and Ovarian Cancer Patients Without Prior Genetic Counselling: the
DNA-BONus Study. Eur J
HumGenetic.
2016;24:881-888.
10. Kim R, et al. Incidence of germline BRCA1- and BRCA2-mutated
Breast Cancer in the US. SABCS. 2017;poster P5-08-28.
11. National Breast Cancer Foundation. BRCA: The Breast Cancer
Gene. Available at https://www.nationalbreastcancer.org/what-is-brca.
Accessed February 2021.
12. SEER. SEER Cancer Statistics Review, 1975-2013. Available
at http://seer.cancer.gov/csr/1975_2013/.
Accessed February 2021.
13. Bertozzi S, et al. Biomarkers in Breast
Cancer. Intechopen. 2018.
14. Yersal O, and Barutca S. Biological Subtypes of Breast Cancer:
Prognostic and therapeutic implications. World J Clin
Oncol.
2014;5(3):412-424.
15. Rivenbark A, et al. Molecular and Cellular Heterogeneity in Breast
Cancer: Challenges for Personalized
Medicine. Am J Pathol. 2013;183(4):1113-1124.
16. Roy R, et al. BRCA1 and BRCA2: Different Roles in a Common
Pathway of Genome Protection. Nat Rev
Cancer.
12(1):68-78.
17. Wu J, et al. The Role of BRCA1 in DNA Damage
Response. Protein
Cell.
2010;1(2):117-123.
18. Gorodetska I, et al. BRCA Genes: The Role in Genome Stability, Cancer
Stemness and Therapy Resistance. J Cancer. 2019;10(9):2109-2127.
19. Li H, et al. PARP Inhibitor Resistance: The Underlying
Mechanisms and Clinical Implications. Mol Cancer. 2020;19:107.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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:
17 February
2021
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
|
Title:
Company Secretary
|