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2018-10-21

AstraZeneca: SOLO-1 Phase III trial demonstrates Lynparza maintenance therapy cut risk of disease progression or death by 7...

60% of patients receiving Lynparza remained progression-free at three
years compared to 27% on placebo following platinum-based
chemotherapy

Lynparza is the only PARP inhibitor to demonstrate an improvement in
progression-free survival as 1st-line maintenance treatment for
advanced ovarian cancer

AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known
as MSD outside the US and Canada) today announced detailed results
from the Phase III SOLO-1 trial testing Lynparza (olaparib) tablets
as a maintenance treatment for patients with newly-diagnosed,
advanced BRCA-mutated (BRCAm) ovarian cancer who were in complete or
partial response following 1st-line standard platinum-based
chemotherapy.

Results of the trial confirm the statistically-significant and
clinically-meaningful improvement in progression-free survival (PFS)
for Lynparza compared to placebo, reducing the risk of disease
progression or death by 70% (HR 0.30 [95% CI 0.23-0.41], p<0.001). At
41 months of follow-up, the median PFS for patients treated with
Lynparza was not reached compared to 13.8 months for patients treated
with placebo. Of those receiving Lynparza, 60% remained
progression-free at 36 months compared to 27% of women in the placebo
arm. The data were presented at the Presidential Symposium of the
ESMO 2018 Congress (European Society for Medical Oncology) in Munich,
Germany and published simultaneously online in the New England
Journal of Medicine (NEJM).

Kaplan-Meier estimates of investigator-assessed PFS

[image]

From the New England Journal of Medicine, Moore K, Colombo N, Scambia
G, et al. Maintenance olaparib in patients with newly diagnosed
advanced ovarian cancer. N Engl J Med. DOI: 10.1056/NEJMoa1810858.
Copyright © 2018 Massachusetts Medical Society. Reprinted with
permission from Massachusetts Medical Society.

Summary of PFS1,2

Lynparza (n=260) Placebo (n=130)
Number of patients with event (%)3 102 (39) 96 (73)
Median (in months) Not reached 13.8
Hazard ratio (95% CI) 0.30 (0.23-0.41)
P-value p<0.001

1 Investigator-assessed

2 Median (interquartile range) duration of follow-up 40.7 months
(34.9-42.9) for Lynparza and 41.2 months (32.2-41.6) for placebo

3 Analysis was done at 50.6% maturity

Sean Bohen, Executive Vice President, Global Medicines Development and
Chief Medical Officer, said: "There is currently a significant unmet
need in the treatment of advanced ovarian cancer because 70% of women
relapse within the first three years after their initial treatment.
The remarkable results of the SOLO-1 trial, which showed that 60% of
women with newly-diagnosed, advanced BRCA-mutated ovarian cancer
remained progression-free at three years, highlight the potential of
Lynparza as a maintenance therapy in the 1st-line setting."

Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories, said:
"Our collective goal in oncology research is to improve long-term
outcomes for people living with cancer. Based on the SOLO-1 trial
results, Lynparza is the only PARP inhibitor to have demonstrated a
significant and clinically-meaningful improvement in reducing the
risk of progression for newly-diagnosed patients with advanced
BRCA-mutated ovarian cancer following platinum-based chemotherapy. We
are working with regulatory authorities as quickly as possible to
seek approval of Lynparza for these patients."

Kathleen Moore, Co-Principal Investigator of the SOLO-1 trial and
Associate Director for Clinical Research at the Stephenson Cancer
Center at the University of Oklahoma, Oklahoma City, US, said: "Women
with ovarian cancer are often diagnosed with advanced disease, which
unfortunately is associated with poor long-term survival rates. The
newly-diagnosed setting is our best opportunity to achieve a
sustained remission, since once a patient's ovarian cancer recurs, it
is typically incurable. The SOLO-1 results demonstrate the potential
of Lynparza maintenance therapy earlier in the treatment pathway and
reinforce the importance of identifying a patient's BRCA mutation
status at the time of diagnosis - these results could change the way
we treat women with advanced BRCA-mutated ovarian cancer."

The SOLO-1 safety profile was in line with that observed in prior
clinical trials. The most common adverse events (AEs) ?20% were
nausea (77%), fatigue/asthenia (63%), vomiting (40%), anaemia (39%)
and diarrhoea (34%). The most common ? grade 3 AEs were anaemia (22%)
and neutropenia (9%). Seventy-two percent of patients on Lynparza
remained on the recommended starting dose. Additionally, 88% of
patients on Lynparza continued treatment without an AE-related
discontinuation.

AstraZeneca and MSD are exploring additional trials in ovarian cancer,
including the ongoing GINECO/ENGOTov25 Phase III trial, PAOLA-1. This
trial is testing the effect of Lynparza in combination with
bevacizumab as a maintenance treatment for patients with
newly-diagnosed advanced ovarian cancer, regardless of their BRCA
status. Results are expected during the second half of 2019.

Lynparza is currently approved in over 60 countries for the treatment
of platinum-sensitive relapsed ovarian cancer regardless of BRCA
status and in the US, Canada, Japan and Australia for germline
BRCA-mutated HER2-negative metastatic breast cancer.

About SOLO-1

SOLO-1 is a Phase III randomised, double-blinded, placebo-controlled,
multicentre trial to evaluate the efficacy and safety of Lynparza
tablets (300 mg twice daily) as maintenance monotherapy compared with
placebo, in newly-diagnosed patients with advanced BRCAm ovarian
cancer following platinum-based chemotherapy. The trial randomised
391 patients with a deleterious or suspected deleterious BRCA1 or
BRCA2 mutation who were in clinical complete or partial response
following platinum-based chemotherapy. Patients were randomised (2:1)
to receive Lynparza or placebo for up to two years or until disease
progression (at the investigator's discretion). The primary endpoint
was PFS and key secondary endpoints included time to second disease
progression or death, time to first subsequent treatment and overall
survival.

About Lynparza

Lynparza (olaparib) is a first-in-class PARP inhibitor and the first
targeted treatment to potentially exploit DNA damage response (DDR)
pathway deficiencies, such as BRCA mutations, to preferentially kill
cancer cells. Specifically, in vitro studies have shown that
Lynparza-induced cytotoxicity may involve inhibition of
PARP-enzymatic activity and increased formation of PARP-DNA
complexes, resulting in DNA damage and cancer cell death. Lynparza is
being tested in a range of DDR-deficient tumour types.

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 20,000 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.

About ovarian cancer

Ovarian cancer is a leading cause of cancer death in women worldwide,
with a five-year survival rate of 19%.[i]
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In 2018, there were over 295,000 new cases diagnosed and around
184,799 deaths.[ii]
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For newly-diagnosed advanced ovarian cancer, the primary aim of
treatment is to delay progression of the disease for as long as
possible and maintain the patient's quality of life with the intent
of achieving complete remission or cure.[iii]
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(http://file:///C:/Users/kdzn235/AppData/Local/Microsoft/Windows/INetCach...)

About BRCA mutations

BRCA1 and BRCA2 are human genes that produce proteins responsible for
repairing damaged DNA and play an important role in 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.

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 a key growth driver for AstraZeneca
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 a...

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