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2019-08-07

AstraZeneca: Lynparza Phase III PROfound trial in HRR* mutation-selected metastatic castration-resistant prostate cancer me...

AstraZeneca and MSD's Lynparza met the primary endpoint of
significantly increasing the time patients selected for BRCA1/2 or
ATM mutations live without radiographic disease progression vs.
standard of care treatment

Only PARP inhibitor with positive Phase III results in four different
cancer types (ovarian, breast, pancreatic and prostate)

AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck &
Co., Inc. inside the US and Canada) today announced positive results
from the Phase III PROfound trial of Lynparza (olaparib) in men with
metastatic castration-resistant prostate cancer (mCRPC) who have a
*homologous recombination repair gene mutation (HRRm) and have
progressed on prior treatment with new hormonal anticancer treatments
(e.g. enzalutamide and abiraterone).

Results from the trial showed a statistically-significant and
clinically-meaningful improvement in the primary endpoint of
radiographic progression-free survival (rPFS) with Lynparza vs.
enzalutamide or abiraterone in men with mCRPC selected for BRCA1/2 or
ATM gene mutations, a subpopulation of HRR gene mutations. The safety
and tolerability profile of Lynparza was generally consistent with
previous trials.

José Baselga, Executive Vice President, Oncology R&D, said: "For men
with metastatic castration-resistant prostate cancer the disease
remains deadly, especially in those who have failed on a new hormonal
anticancer treatment. This trial is the only positive Phase III trial
of any PARP inhibitor in metastatic castration-resistant prostate
cancer, where the need for new, effective therapies is high. The
PROfound trial also demonstrates the potential value of genomic
testing in this at-risk patient population. We look forward to
discussing these results with global health authorities soon."

Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories, said:
"Metastatic castration-resistant prostate cancer is a deadly disease
and represents an area of critical unmet medical need. The Phase III
PROfound trial is another example of MSD and AstraZeneca's shared
commitment to improving long-term outcomes for people living with
cancer. These results represent the potential for a new, oral
targeted treatment option for this patient population."

AstraZeneca and MSD plan to present the full data from the trial at a
forthcoming medical meeting. The companies are also exploring
additional trials in prostate cancer, including the ongoing Phase III
PROpel trial, testing Lynparza as a 1st-line therapy in mCRPC, in
combination with abiraterone.

About PROfound

PROfound is a prospective, multicentre, randomised, open-label, Phase
III trial testing the efficacy and safety of Lynparza versus
enzalutamide or abiraterone in patients with mCRPC who have
progressed on prior treatment with new hormonal anticancer treatments
and have a qualifying tumour mutation in one of 15 genes involved in
the HRR pathway, including among them BRCA1/2, ATM and CDK12.

About metastatic castration-resistant prostate cancer

Prostate cancer is the second-most common cancer in men, with an
estimated 1.3 million new cases diagnosed worldwide in 2018 and is
associated with a significant mortality rate.[1] Development of
prostate cancer is often driven by male sex hormones called
androgens, including testosterone.[2] mCRPC occurs when 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.[2] Approximately 10-20% of men with advanced prostate
cancer will develop CRPC within five years, and at least 84% of these
will have metastases at the time of CRPC diagnosis.[3] Of men with no
metastases at CRPC diagnosis, 33% are likely to develop metastases
within two years.[3] Despite an increase in the number of available
therapies for men with mCRPC, five-year survival remains low.[3]

About 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 64 countries, including those in the
EU, for the maintenance treatment of platinum-sensitive relapsed
ovarian cancer regardless of BRCA status. It is approved in the US,
EU, Japan and several other countries as 1st-line maintenance
treatment of BRCAm advanced ovarian cancer following response to
platinum-based chemotherapy. It is also approved in 40 countries,
including the US and Japan, for germline BRCAm HER2-negative
metastatic breast cancer previously treated with chemotherapy; in the
EU this includes locally advanced breast cancer. Regulatory reviews
are underway in other jurisdictions for ovarian, breast and
pancreatic cancers.

Lynparza, which is being jointly developed and commercialised by
AstraZeneca and MSD, is approved for advanced ovarian cancer and
metastatic breast cancer and has been used in over 25,000 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.

In January 2016, AstraZeneca announced
(https://www.astrazeneca.com/media-centre/press-releases/2016/Lynparza-Ol...)
that Lynparza was granted Breakthrough Therapy Designation by the US
Food and Drug Administration (FDA) for the monotherapy treatment of
BRCA1/2- or ATM gene-mutated mCRPC in patients who have received a
prior taxane-based chemotherapy and at least one newer hormonal agent
(abiraterone or enzalutamide), based on the positive results of the
TOPARP-A Phase II trial.

About the AstraZeneca and MSD strategic oncology collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US,
known as MSD outside the United States and Canada, announced a global
strategic oncology collaboration to co-develop and co-commercialise
Lynparza, the world's first PARP inhibitor, and potential new
medicine selumetinib, a MEK inhibitor, for multiple cancer types.
Working together, the companies will develop Lynparza and selumetinib
in combination with other potential new medicines and as
monotherapies. Independently, the companies will develop Lynparza and
selumetinib in combination with their respective PD-L1 and PD-1
medicines.

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, we are
committed to advance Oncology as one of AstraZeneca's four 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, 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 (http://www.astrazeneca.com/) and follow us on
Twitter @AstraZeneca (https://twitter.com/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
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Malmberg
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Investor
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Larsen
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Gruvris (cardiovascular,
metabolism)
Nick Stone BioPharmaceuticals +44 203 749 5716
(respiratory, renal)
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References

1. World Health Organisation. International Agency for Research on
Cancer. Global Cancer Statistics 2018 estimates of incidence and
mortality worldwide for 36 cancers in 185 countries
https://gco.iarc.fr/ [Accessed July 2019].

2.[ ]Cancer.Net. (2019). Treatment of metastatic castration-resistant
prostate cancer.

https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-rec...
[Accessed July 2019].

3.[ ]Cancer.Net. (2019). Prostate Cancer - Statistics. Available at:
www.cancer.net/cancer-types/prostate-cancer/statistics [Accessed July
2019].

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