astrazenecaplcmasterform6
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 April 2023
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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INDEX
TO EXHIBITS
1.
Lynparza + Imfinzi met endpoint in ovarian
cancer
5 April
2023 07:00 BST
Lynparza and Imfinzi combination improved
progression-free survival in newly diagnosed patients with advanced
ovarian cancer without tumour BRCA mutations in DUO-O Phase III
trial
Positive
high-level results from a planned interim analysis of the DUO-O
Phase III trial showed treatment with a combination of Lynparza (olaparib), Imfinzi (durvalumab), chemotherapy and
bevacizumab demonstrated a statistically significant and clinically
meaningful improvement in progression-free survival (PFS) versus
chemotherapy plus bevacizumab (control arm) in newly diagnosed
patients with advanced high-grade epithelial ovarian cancer without
tumour BRCA mutations. Patients were treated with Imfinzi in combination with
chemotherapy and bevacizumab followed by Imfinzi, Lynparza and bevacizumab as maintenance
therapy.
In an
additional arm, Imfinzi,
chemotherapy plus bevacizumab showed a numerical improvement in PFS
versus the control arm but did not reach statistical significance
at this interim analysis.
At the
time of this planned interim analysis, the overall survival (OS)
and other secondary endpoints are immature and will be formally
assessed at a subsequent analysis.
Ovarian
cancer is one of the most common gynaecologic cancers.1 Over two thirds of
patients are diagnosed with advanced disease which can progress
quickly, often within two years, diminishing their quality of life
despite treatment. Unfortunately, 50-70% of patients with advanced
disease die within five years.2-5
Philipp
Harter, Director, Department of Gynaecology and Gynaecologic
Oncology, Evangelische Kliniken Essen-Mitte, Germany and principal
investigator for the trial, said: "DUO-O showcases the power of
academia and industry collaboration in advancing new treatment
combinations for patients with ovarian cancer. I’m grateful
for the academic cooperative study groups and patients around the
world that made this trial possible and look forward to sharing the
results with the clinical community."
Susan
Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "While there has been significant progress for patients with
advanced ovarian cancer, an unmet need still remains. These data
from the DUO-O trial provide encouraging evidence for this
Lynparza and Imfinzi combination in patients without
tumour BRCA mutations and reinforce our continued commitment to
finding new treatment approaches for these patients. It will be
important to understand the key secondary endpoints as well as data
for relevant subgroups.”
The safety and tolerability of these combinations
are broadly consistent with that
observed in prior clinical trials and the known profiles of the
individual medicines.
The data will be presented at forthcoming medical meetings and
shared with health authorities.
Notes
Ovarian cancer
Ovarian
cancer is the eighth most common cancer in women worldwide with
more than 314,000 new patients diagnosed with ovarian cancer in
2020 and over 207,000 deaths. This number is expected to rise by
almost 42% by 2040 to over 445,000 newly diagnosed patients and
314,000 deaths.6
DUO-O
DUO-O
is a Phase III randomised, double-blind, placebo-controlled,
multi-centre trial to evaluate the efficacy and safety of
Imfinzi in combination with
platinum-based chemotherapy and bevacizumab followed by maintenance
treatment with Imfinzi and
bevacizumab with or without Lynparza in newly diagnosed patients
with advanced ovarian cancer without tumour BRCA
mutations.
Patients
were randomized 1:1:1 to: Arm 1 (control), induction therapy with
platinum-based chemotherapy in combination with bevacizumab and
placebo followed by maintenance treatment with bevacizumab plus
placebo; Arm 2, induction therapy with platinum-based chemotherapy
in combination with bevacizumab and Imfinzi followed by maintenance
Imfinzi and bevacizumab
plus placebo; or Arm 3, induction therapy with platinum-based
chemotherapy in combination with bevacizumab and Imfinzi followed by maintenance
Imfinzi and
bevacizumab plus
Lynparza. In all arms,
platinum-based chemotherapy was administered every 3 weeks (q3w)
for up to 6 cycles, bevacizumab was administered q3w for up to 15
months, Imfinzi or placebo
was administered q3w for up to 24 months, and Lynparza or placebo was administered
twice daily for up to 24 months.
The
primary endpoint of the trial is PFS as assessed by investigator
for Arm 3 compared to Arm 1 (control) in the overall trial
population which included patients without tumour BRCA mutations
and in the subset of these patients with HRD positive disease. Key
secondary endpoints include PFS as assessed by investigator in Arm
2 compared to control, as well as comparisons for OS. DUO-O
enrolled over 1200 patients across all treatment arms at 179 study
locations. For more information about the trial, visit ClinicalTrials.gov.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that
binds to the PD-L1 protein and blocks the interaction of PD-L1 with
the PD-1 and CD80 proteins, countering the tumour's immune-evading
tactics and releasing the inhibition of immune
responses.
Imfinzi is the only approved immunotherapy and the global
standard of care in the curative-intent setting of unresectable,
Stage III non-small cell lung cancer (NSCLC) in patients whose
disease has not progressed after chemoradiation therapy based on
the PACIFIC Phase III trial. Imfinzi is also approved in the US, EU,
Japan, China and many other countries around the world for the
treatment of extensive-stage small cell lung cancer (SCLC) based on
the CASPIAN Phase III trial. Additionally, Imfinzi is approved in combination with
a short course of Imjudo
(tremelimumab) and chemotherapy for the treatment of metastatic
NSCLC in the US, EU and Japan based on the POSEIDON Phase III
trial.
In
addition to its indications in lung cancer, Imfinzi is also approved in combination
with chemotherapy in
locally advanced or metastatic biliary tract cancer in the US, EU,
Japan and several other countries; in combination with Imjudo in unresectable hepatocellular
carcinoma in the US, EU and Japan; and in previously treated
patients with advanced bladder cancer in a small number of
countries.
Since
the first approval in May 2017, more than 150,000 patients have
been treated with Imfinzi.
As part of a broad development programme, Imfinzi is being tested as a single
treatment and in combinations with other anti-cancer treatments for
patients with SCLC, NSCLC, bladder cancer, several gastrointestinal
cancers, ovarian cancer, endometrial cancer and other solid
tumours.
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 new
hormonal agents [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
currently approved in a number of countries across multiple tumour
types including maintenance treatment of platinum-sensitive
relapsed ovarian cancer and as both monotherapy and in combination
with bevacizumab for the 1st-line maintenance treatment of
BRCA-mutated (BRCAm) and homologous recombination deficiency
(HRD)-positive advanced ovarian cancer, respectively; for germline
BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer (in
the EU and Japan this includes locally advanced breast cancer); for
gBRCAm, HER2-negative high-risk early breast cancer (in Japan this
includes all BRCAm HER2-negative high-risk early breast cancer);
for gBRCAm metastatic pancreatic cancer; in combination with
abiraterone for the treatment of metastatic castration-resistant
prostate cancer (mCRPC) in whom chemotherapy is not clinically
indicated (in the EU) and as monotherapy in HRR gene-mutated mCRPC
in patients who have progressed on prior NHA treatment
(BRCAm only in the EU and
Japan). In China, Lynparza is approved for the treatment
of BRCA-mutated mCRPC, as a 1st-line maintenance therapy in
BRCA-mutated advanced ovarian cancer as well as 1st-line
maintenance treatment with bevacizumab for HRD-positive advanced
ovarian cancer.
Lynparza, which is being jointly developed and
commercialised by AstraZeneca and MSD, has been used to treat over
75,000 patients worldwide. The companies develop Lynparza in combination with their
respective PD-L1 and PD-1 medicines independently. Lynparza is the foundation of
AstraZeneca's industry-leading portfolio of potential new medicines
targeting DDR mechanisms in cancer cells.
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.
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
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details on how to contact the Investor Relations Team, please click
here. For Media
contacts, click here.
References
1.
Momenimovahed Z,
et al. Ovarian Cancer in
the World: Epidemiology and Risk Factors. Int J Womens Health. 2019 Apr
30;11:287-299.
2.
National Cancer
Institute. Cancer Stat Facts: Ovarian Cancer. Available at
https://seer.cancer.gov/statfacts/html/ovary.html.
Accessed March 2023.
3.
Ray-Coquard,
et al. Final Overall
Survival (OS) Results from the Phase III PAOLA-1/ENGOT-ov25 Trial
Evaluating Maintenance Olaparib (ola) plus Bevacizumab (bev) in
Patients (pts) with Newly Diagnosed Advanced Ovarian Cancer (AOC).
Presented at the European Society of Medical Oncology Congress.
Paris, France. 09 September 2022.
4.
Ray-Coquard I,
et al. Olaparib Plus
Bevacizumab as First-Line Maintenance in Ovarian Cancer.
N Engl J Med. 2019;
381:2416-2428
5.
González-Martín
A, et al. Niraparib in
Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019;
381:2391-2402
6.
World Cancer
Research Fund International. Ovarian Cancer Statistics. Available
at https://www.wcrf.org/cancer-trends/ovarian-cancer-statistics/#:~:text=Latest%20ovarian%20cancer%20data,of%20ovarian%20cancer%20in%202020.
Accessed March 2023.
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: 5
April 2023
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By: /s/
Adrian Kemp
|
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Name:
Adrian Kemp
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|
Title:
Company Secretary
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