a8809m
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 September 2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza
PROpel trial meets primary endpoint
This announcement contains inside information
24 September 2021 07:00 BST
Lynparza in combination with abiraterone
significantly delayed disease progression in all-comers in PROpel
Phase III trial in
1st-line metastatic castration-resistant prostate
cancer
First PARP inhibitor to demonstrate clinical benefit
in
combination with a new hormonal agent in this setting
Positive high-level results from the PROpel Phase III trial showed
AstraZeneca and MSD's Lynparza (olaparib) in combination with abiraterone
demonstrated a statistically significant and clinically meaningful
improvement in radiographic progression-free survival (rPFS) versus
standard-of-care abiraterone as a 1st-line treatment for men with
metastatic castration-resistant prostate cancer (mCRPC) with or
without homologous recombination repair (HRR) gene
mutations.
At a planned interim analysis, the Independent Data Monitoring
Committee (IDMC) concluded that the trial met the primary endpoint
of rPFS in men with mCRPC who had not received treatment in
the 1st-line setting including with new hormonal agents (NHAs) or
chemotherapy.
The trial also showed a trend at this interim analysis towards
improved overall survival (OS). However, the data are still
immature and the trial will continue to assess OS as a key
secondary endpoint. The safety and tolerability were consistent
with the known profiles of each medicine.
Prostate cancer is the second-most common cancer in men and despite
an increase in the number of available treatments for men with
mCRPC, five-year survival remains low.1
Susan Galbraith, Executive Vice President, Oncology R&D, said:
"Today, men with metastatic castration-resistant prostate cancer
have limited options in the 1st-line setting, and sadly often the
disease progresses after initial treatment with current standards
of care. These exciting results demonstrate the potential
for Lynparza with abiraterone to become a new 1st-line
option for patients regardless of their biomarker status and reach
a broad population of patients living with this aggressive disease.
We look forward to discussing the results with global health
authorities as soon as possible."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "We are encouraged by the PROpel results and the clinical
benefit Lynparza in combination with abiraterone demonstrated
versus abiraterone alone as a 1st-line treatment option for men
with metastatic castration-resistant prostate cancer. Today's
results build on MSD and AstraZeneca's commitment to
bring Lynparza earlier in lines of treatment and to more
patients with advanced prostate cancer."
The data will be presented at an upcoming medical
meeting.
Metastatic castration-resistant prostate cancer
Metastatic prostate cancer is associated with a significant
mortality rate.2 Development
of prostate cancer is often driven by male sex hormones called
androgens, including testosterone.3
In patients with mCRPC, their prostate cancer grows and spreads to
other parts of the body despite the use of androgen-deprivation
therapy to block the action of male sex
hormones.3 Approximately
10-20% of men with advanced prostate cancer will develop CRPC
within five years, and at least 84% of these men will have
metastases at the time of CRPC diagnosis.4
Of men with no metastases at CRPC diagnosis, 33% are likely to
develop metastases within two years.4 Despite
advances in treatment for men with mCRPC, five-year survival is low
and extending survival remains a key treatment
goal.4
PROpel
PROpel is
a randomised, double-blind, multi-centre Phase
III trial testing the efficacy, safety, and tolerability
of Lynparza versus placebo when given in addition to
abiraterone in men with mCRPC who had not received prior
chemotherapy or NHAs in the 1st-line setting. Men in both treatment
groups will also receive either prednisone or prednisolone twice
daily. The primary endpoint is rPFS and secondary endpoints include
OS and time to first subsequent anticancer therapy or
death.
The trial enrolled men with or without HRR gene mutations. They may
have previously been treated with docetaxel at a prior stage of
disease. The trial excluded men with prior treatment with
abiraterone. Treatment with any other NHA must have been stopped
one year or longer prior to randomisation.
Men must have had a performance status of 0-1 as defined by the
Eastern Cooperative Oncology Group (ECOG) criteria and be a
candidate for abiraterone treatment with documented evidence of
progressive disease.
Preclinical trials in prostate cancer report a combined anti-tumour
effect when PARP inhibitors and NHAs are administered together.
PARP-1 is involved in the co-regulation of the androgen-receptor
(AR) pathway, potentially leading to cooperation between PARP
inhibitors and NHAs in blocking AR signalling.5
PARP inhibition plus androgen deprivation could significantly
reduce the growth of prostate cancer cells independent of HRR gene
status. Other trials revealed that treatment with NHAs inhibit the
transcription of some HRR genes, therefore, inducing HRR deficiency
and increased sensitivity to PARP inhibitors via non-genetic
mechanisms. 6
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 those
with mutations in BRCA1 and/or BRCA2, or those where deficiency is
induced by other agents (such as NHAs).
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
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 germline BRCAm 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 oncology
AstraZeneca is leading a revolution in oncology with the ambition
to provide cures for cancer in every form, following the science to
understand cancer and all its complexities to discover, develop and
deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It
is through persistent innovation that AstraZeneca has built one of
the most diverse portfolios and pipelines in the industry, with the
potential to catalyse changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care 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 in
Oncology, Rare Diseases, and BioPharmaceuticals, including
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
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References
1. IARC. Cancer Today - Estimated number of new cases in 2020,
worldwide, both sexes, all ages. Available
at: https://gco.iarc.fr/today/home.
Accessed September 2021.
2. Bray et al. Global cancer statistics 2018: GLOBOCAN estimates of
incidence and mortality worldwide for 36 cancers in 185
countries. CA: A Cancer Journal for
Clinicians. 2018;68(6),pp394-424.
3. Cancer.Net. Treatment of metastatic castration-resistant
prostate cancer. Available at: www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer.
Accessed September 2021.
4. Kirby, M., et al. Characterising the castration-resistant
prostate cancer population: a systematic
review. International Journal of
Clinical Practice,
2021;65(11),pp1180-1192.
5. Schiewer, M., et al. Dual roles of PARP-1 promote cancer growth
and progression. Cancer Discov. 2012;2(12),pp 1134-49
6. Polkinghorn, W., et al. Androgen receptor signaling regulates
DNA repair in prostate cancers. Cancer Discov.
2013;3(11):1245-53
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:
24 September 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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