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 May 2023
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Imfinzi + Lynparza prolonged PFS in endometrial cancer when added
to chemotherapy
26 May 2023
Imfinzi plus Lynparza and Imfinzi alone
both significantly improved progression-free survival in advanced
endometrial cancer when added to chemotherapy
DUO-E is the first global Phase III trial of immunotherapy
plus
PARP inhibition to demonstrate clinical benefit in this
setting
Positive high-level results from the DUO-E Phase III trial
showed Imfinzi (durvalumab) in combination with
platinum-based chemotherapy followed by
either Imfinzi plus Lynparza (olaparib) or Imfinzi alone as
maintenance therapy
both demonstrated a
statistically significant and clinically meaningful improvement in
progression-free survival (PFS) compared to standard-of-care
chemotherapy alone in
patients with newly diagnosed advanced or recurrent endometrial
cancer. There was a greater clinical benefit observed with the
combination of Imfinzi and Lynparza as maintenance
treatment.
Overall survival (OS) data were immature at the time of this
analysis however, a favourable trend was observed for both
treatment regimens.
Endometrial cancer is the 6th most common cancer in women
worldwide, with over 417,000 patients diagnosed and over 97,000
deaths in 2020.1 Diagnoses
are expected to rise by almost 40% by 2040.2 The
current standard of care for advanced endometrial cancer is
chemotherapy.3,4 However,
long-term outcomes in 1st-line endometrial cancer remain poor and
novel treatment options are needed.5,6
Shannon N. Westin, Professor of Gynaecologic Oncology and
Reproductive Medicine at the University of Texas MD Anderson Cancer
Center, and principal investigator of the DUO-E trial, said: "These
exciting data demonstrate durvalumab immunotherapy can
significantly delay disease progression for patients with
endometrial cancer and the addition of the PARP inhibitor olaparib
can improve the benefit further. These combinations could provide
physicians with new treatment approaches to improve outcomes for
patients."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "These DUO-E data demonstrate for the first time
the power of combining immunotherapy and a PARP inhibitor to
provide meaningful clinical improvements for patients with
endometrial cancer. These
results underscore our ambition to redefine cancer care
and we
hope to bring this innovative Imfinzi and Lynparza combination to endometrial cancer patients
as soon as possible."
The safety and tolerability profile of Imfinzi plus chemotherapy and
of Imfinzi in combination with Lynparza was broadly consistent with that observed in
prior clinical trials and the known profiles of the individual
medicines.7,8
These data will be presented at a forthcoming medical meeting, and
we look forward to discussing them with health
authorities.
Notes
Endometrial cancer
Endometrial cancer is a highly heterogenous disease that originates
in the tissue lining of the womb and is most common in women who
have already been through the menopause, with the average age at
diagnosis being over 60 years old.9-11 Both
the incidence and mortality of endometrial cancer are expected to
increase from 417,400 cases and 97,400 deaths in 2020 to 608,130
cases and 157,813 deaths in 2040.1,2
The majority of patients with endometrial cancer are diagnosed at
an early stage of disease where the cancer is confined to the
uterus. They are typically treated with surgery and/or radiation
and the 5-year survival rate is high (approximately 95%). However,
patients with advanced disease (Stage III-IV) are usually treated
with chemotherapy and have a much poorer prognosis, with a 5-year
survival rate falling to around 20-30%.4,5,11,12,13
For patients where the disease has already advanced or returned,
treatment options are limited as the cancer is not considered
likely to respond to hormonal therapy and will be treated with
chemotherapy.5,6
DUO-E
The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised,
double-blind, placebo-controlled, multicentre Phase III trial of
1st-line Imfinzi in combination with platinum-based
chemotherapy (carboplatin and paclitaxel) followed
by Imfinzi with Lynparza or Imfinzi alone as maintenance therapy versus
platinum-based chemotherapy alone as a treatment for patients with
newly diagnosed advanced or recurrent endometrial
cancer.
The DUO-E trial randomised 699 patients with newly diagnosed or
recurrent Stage III or IV epithelial endometrial carcinoma
(excluding sarcomas) to receive either 1120mg
of Imfinzi or placebo, given every three weeks in
combination with standard-of-care platinum-based chemotherapy.
Following cessation of chemotherapy, patients were given either
1500mg of Imfinzi or placebo every four weeks as maintenance,
either in combination with 300mg BID (2x150mg tablets, twice a day)
of Lynparza or placebo until progressive disease for 24
months.
The dual primary endpoint was PFS. Mismatch repair (MMR) status was
one of the stratification factors. Key secondary endpoints included
OS, objective response rate (ORR), duration of response (DoR) and
safety and tolerability. The trial was conducted in 253 study
locations across 22 countries including the US, Europe, South
America and Asia.
For more information about the trial please
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 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-related (HRR) genes, 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 repair deficient
(HRD)-positive advanced ovarian cancer, respectively; for germline
BRCA mutation (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 in whom chemotherapy is not clinically indicated
(EU only) and as monotherapy for HRR gene-mutated metastatic
castration-resistant prostate cancer 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 metastatic castration-resistant prostate cancer as
well as a 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 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
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. World Cancer Research Fund
International. Endometrial Cancer Statistics. Available
at https://www.wcrf.org/cancer-trends/endometrial-cancer-statistics/.
Accessed May 2023.
2. IARC. WHO. Corpus Uteri. Estimated
Numbers From 2020 To 2040, Females, Age [0-85+] World. Available
at: https://gco.iarc.fr/tomorrow/en/dataviz/trends Accessed
May 2023.
3. Carlson R. Advanced Endometrial
Cancer Carboplatin-Paclitaxel Regimen
Promising. Oncology
Times.
2003;25(22):36.
4. Ferris JS, et al. Uterine Serous
Carcinoma: Key Advances and Novel Treatment
Approaches. International Journal of
Gynecological Pathology.
2021;31(8):1165-1174.
5. Matrai CE, et al. Molecular
Evaluation of Low-grade Low-Stage Endometrial Cancer with and
Without Recurrence. International Journal of
Gynecological Pathology.
2022;41(3):207-219.
6. Soumerai T, et al. Clinical Utility
of Prospective Molecular Characterization in Advanced Endometrial
Cancer. Clin Cancer
Res. 2018 Dec
1;24(23):5939-5947.
7. FDA. Highlights of prescribing
information - Lynparza. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208558s014lbl.pdf.
Accessed May 2023.
8. FDA. Highlights of prescribing
information - Imfinzi. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761069s018lbl.pdf.
Accessed May 2023.
9. Dork T, et al. Genetic Susceptibility to Endometrial Cancer:
Risk Factors and Clinical Management. Cancers (Basel). 2020
Sep;12(9):2407.
10. American Cancer Society. What is
Endometrial Cancer? Available at https://www.cancer.org/cancer/endometrial-cancer/about/what-is-endometrial-cancer.html. Accessed
May 2023.
11. Oakin A, et al. ESMO Guidelines. Endometrial Cancer: ESMO
Clinical Practice Guidelines for Diagnosis, Treatment and
Follow-Up. Ann Oncol. 2022 Sep;33(9):860-877.
12. Wright JD, et al. Contemporary Management of Endometrial
Cancer. Lancet. 2012 Apr
7;379(9823):1352-60.
13. Monk BJ, et al. Real-World Outcomes in Patients with
Advanced Endometrial Cancer: A Retrospective Cohort Study of US
Electronic Health Records. Gynecologic
Oncology.
2022;164(2):325-332.
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:
26 May 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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