astrazenecaplc-4507u
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 July 2024
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
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United
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza & Imfinzi positive CHMP in endometrial
1 July 2024
Lynparza and Imfinzi combination
recommended for approval in the EU by CHMP for patients with
mismatch repair proficient advanced or recurrent endometrial
cancer
Imfinzi also recommended for patients with mismatch repair
deficient disease
Recommendation based on DUO-E Phase III results, which showed both
regimens demonstrated statistically significant and clinically
meaningful improvement in progression-free survival vs.
chemotherapy alone
AstraZeneca's Imfinzi (durvalumab) and Lynparza (olaparib) have been recommended for
approval in the European Union (EU) as treatment for certain
patients with primary advanced or recurrent endometrial
cancer. Imfinzi plus chemotherapy as 1st-line treatment
followed by Lynparza and Imfinzi has been recommended for patients with
mismatch repair proficient (pMMR) disease. Imfinzi plus chemotherapy followed
by Imfinzi alone has been recommended for patients with
mismatch repair deficient (dMMR) disease.
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) based its positive opinion
on a prespecified exploratory subgroup analysis
by mismatch repair (MMR) status
from the DUO-E Phase
III trial, which was
published in the Journal
of Clinical Oncology in
October 2023.
This analysis showed a reduction in the risk of disease progression
or death for pMMR patients in the Lynparza and Imfinzi arm by 43% (median 15.0 months versus 9.7
months, hazard ratio [HR] 0.57; 95% confidence interval [CI]
0.44-0.73) versus the control arm.1 Results
for dMMR patients showed a reduction in the risk of disease
progression or death in the Imfinzi arm by 58% (median not reached versus 7.0
months, HR 0.42; 95% CI 0.22-0.80) versus the control
arm.1
In Europe, endometrial cancer is the fourth most common cancer in
women, with nearly 125,000 diagnoses and more than 30,000 deaths in
2022.2,3 Patients
diagnosed at an early stage of disease have a five-year survival
rate of approximately 80-90%, but that falls to less than 20% for
people with advanced disease.4,5 There
is a significant need for new treatment options, especially for the
70-80% of patients with pMMR disease.5,6 This
recommendation underscores the importance of MMR testing at point
of diagnosis, which is well established and widely
available.7,8
Els Van Nieuwenhuysen, Gynaecological Oncologist at the UZ Leuven,
Belgium and trial investigator, said: "Patients with advanced
or recurrent endometrial cancer currently have a very poor
prognosis, especially those with mismatch repair proficient
disease. This recommendation underscores the significant benefit
shown with durvalumab as well as with the olaparib and durvalumab
combination for patients with both mismatch repair deficient and
mismatch repair proficient status. This marks an important step
toward improving outcomes for these patients in
Europe."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "Today's recommendation for approval in the EU
recognises the potential of the Lynparza and Imfinzi combination to provide clinical benefit for
patients with endometrial cancer, especially for those with
mismatch repair proficient disease who have few available
treatments today. If approved, patients in Europe will have a new
option for combination treatment that brings the additional benefit
of PARP inhibition to immunotherapy."
The safety profiles of both experimental regimens were manageable,
well-tolerated and broadly consistent with the known profiles of
the individual agents.1,9,10
Regulatory submissions for Imfinzi and Lynparza are currently under review in Japan and
several other countries based on the DUO-E
trial. Imfinzi plus chemotherapy was recently approved for
dMMR patients with primary advanced or recurrent endometrial cancer
in the US.11
Notes
Endometrial cancer
Endometrial cancer is a highly heterogeneous disease that
originates in the tissue lining of the uterus and is most common in
women who have already been through menopause, with the average age
at diagnosis being over 60 years old.12-15
The majority of patients with endometrial cancer are diagnosed at
an early stage of disease, where the cancer is confined to the
uterus.16 They
are typically treated with surgery and/or radiation, and the
five-year survival rate is high (approximately
80-90%).17 Patients
with advanced disease (Stage III-IV) usually have a much poorer
prognosis, with the five-year survival rate falling to less than
20%.4 Immunotherapy
combined with chemotherapy is emerging as a new standard of care
for advanced endometrial cancer, particularly for patients with
dMMR disease, who make up approximately 20-30% of all
patients.11,17-20 There
remains a high unmet need for treatments for the remaining 70-80%
of endometrial cancer patients with pMMR
disease.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 (durvalumab) plus platinum-based
chemotherapy (carboplatin and paclitaxel) followed by
either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) 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
advanced or recurrent epithelial endometrial carcinoma to receive
either Imfinzi (1120mg) or placebo, given every three weeks
in addition to standard-of-care platinum-based chemotherapy. After
4-6 cycles of chemotherapy, patients (whose disease had not
progressed) then received either Imfinzi (1500mg) or placebo every four weeks as
maintenance, plus 300mg Lynparza (300mg BID [2x150mg tablets, twice a day])
or placebo until disease progression.
The dual primary endpoint was progression-free survival (PFS) of
each treatment arm versus standard of care. Key secondary
endpoints included overall survival (OS), safety and tolerability.
The trial continues to assess OS for both Imfinzi monotherapy and Imfinzi plus Lynparza as maintenance therapy in the overall trial
population. Mismatch repair (MMR) status, recurrence status and
geographic location were stratification factors. The trial was
sponsored independently by AstraZeneca and 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. Imfinzi is also approved for the treatment of
extensive-stage small cell lung cancer (SCLC) and in combination
with a short course of Imjudo (tremelimumab) and chemotherapy for the
treatment of metastatic NSCLC.
In addition to its indications in lung
cancers, Imfinzi is approved in combination with
chemotherapy (gemcitabine plus cisplatin) in locally
advanced or metastatic biliary tract cancer and in combination
with Imjudo in unresectable hepatocellular carcinoma
(HCC). Imfinzi is also approved as a monotherapy in
unresectable HCC in Japan and the EU.
Since the first approval in May 2017, more than 220,000 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, breast cancer, several
gastrointestinal cancers and other solid
tumours.
Lynparza
Lynparza 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 may also help enhance immunogenicity and
increase the impact of anti-tumour immune
responses.
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
(mCRPC) when chemotherapy is not clinically indicated (EU
only) and for BRCAm mCRPC
(US and Japan); and as monotherapy for
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 well as 1st-line maintenance treatment with
bevacizumab for HRD-positive advanced ovarian
cancer.
Lynparza is being jointly
developed and commercialised by AstraZeneca and MSD, both as a
monotherapy and in combination with other potential medicines.
Independently, the companies are developing and will
commercialise Lynparza in combination with their respective PD-L1
and PD-1 medicines, Imfinzi (durvalumab) and Keytruda (pembrolizumab). Lynparza has been used to treat approximately 140,000
patients worldwide. Lynparza has a broad clinical trial development
programme, 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.
AstraZeneca in immuno-oncology (IO)
AstraZeneca
is a pioneer in introducing the concept of immunotherapy into
dedicated clinical areas of high unmet medical need. The Company
has a comprehensive and diverse IO portfolio and pipeline anchored
in immunotherapies designed to overcome evasion of the anti-tumour
immune response and stimulate the body's immune system to attack
tumours.
AstraZeneca aims to reimagine cancer care and help
transform outcomes for patients with Imfinzi as monotherapy and in combination
with Imjudo as well as other novel immunotherapies and
modalities. The Company is also exploring next-generation
immunotherapies like bispecific antibodies and therapeutics that
harness different aspects of immunity to target
cancer.
AstraZeneca
is boldly pursuing an innovative clinical strategy to bring
IO-based therapies that deliver long-term survival to new settings
across a wide range of cancer types. With an extensive clinical
programme, the Company also champions the use of IO treatment in
earlier disease stages, where there is the greatest potential for
cure.
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's innovative
medicines are sold in more than 125 countries and used by millions
of patients worldwide. Please visit astrazeneca.com and
follow the Company on social media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Westin SN, et al. Durvalumab plus carboplatin/paclitaxel followed
by maintenance durvalumab with or without olaparib as first-line
treatment for advanced endometrial cancer: The phase III DUO-E
trial. Journal of Clinical
Oncology.
2023;42(3):283-299.
2. World Health Organization. IARC.
Absolute numbers, Incidence, Females, in 2022. Europe. Available
at: https://gco.iarc.fr/today/en/dataviz/pie?mode=cancer&cancers=24&sexes=2&group_populations=1&populations=908.
Accessed June 2024.
3. World Health Organization. IARC.
Estimated numbers from 2022 to 2050, Females, age [0-85+]. Europe.
Available at: https://gco.iarc.fr/tomorrow/en/dataviz/trends?types=0_1&sexes=2&mode=cancer&group_populations=0&multiple_populations=0&multiple_cancers=1&cancers=24&populations=908.
Accessed June 2024.
4. Cao SY, et al. Recurrence and survival of patients with
stage III endometrial cancer after radical surgery followed by
adjuvant chemo- or chemoradiotherapy: A systematic review and
meta-analysis. BMC Cancer. 2023;23:31.
5. Kelkar SS, et al. Treatment patterns and real-world clinical
outcomes in patients with advanced endometrial cancer that are
non-microsatellite instability high (Non-MSI-high) or mismatch
repair proficient (pMMR) in the United
States. Gynecologic Oncology
Reports. 2022;42:101026.
6. Yang Y, et al. Molecular subtypes of endometrial cancer:
Implications for adjuvent treatment
strategies. International Journal of
Gynecology & Obstetrics. 2024;164:436-459.
7. Abu-Rustum
N, et
al. Uterine neoplasms,
Version 1.2023, NCCN Clinical Practice Guidelines in
oncology. Journal of the National
Comprehensive Cancer Network.
2023;21(2):181-209.
8. Stelloo E, et al. Practical guidance for mismatch
repair-deficiency testing in endometrial
cancer. Annals of
Oncology. 2017;28(1):96-102.
9. Lynparza SmPC. Available
at: https://www.ema.europa.eu/en/documents/product-information/lynparza-epar-product-information_en.pdf.
Accessed June 2024.
10. Imfinzi SmPC. Available
at: https://www.ema.europa.eu/en/documents/product-information/imfinzi-epar-product-information_en.pdf.
Accessed June 2024.
11. FDA. FDA approves durvalumab with
chemotherapy for mismatch repair deficient primary advanced or
recurrent endometrial cancer. Available
at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-chemotherapy-mismatch-repair-deficient-primary-advanced-or-recurrent.
Accessed June 2024.
12. Dork T, et al. Genetic susceptibility to endometrial
cancer: Risk factors and clinical
management. Cancers. 2020;12(9):2407.
13. Oakin A, et al. Endometrial cancer: ESMO clinical practice
guidelines for diagnosis, treatment and
follow-up. Annals of
Oncology. 2022;33(9):860-877.
14. American Cancer Society. What is
endometrial cancer? Available at https://www.cancer.org/cancer/endometrial-cancer/about/what-is-endometrial-cancer.html.
Accessed June 2024.
15. American Cancer Society. Key statistics
for endometrial cancer. Available at: https://www.cancer.org/cancer/types/endometrial-cancer/about/key-statistics.html.
Accessed June 2024.
16. National Cancer Institute. SEER. Cancer
stat facts: Uterine cancer. Available at: https://seer.cancer.gov/statfacts/html/corp.html.
Accessed June 2024.
17. Hamoud BH, et al. The evolving landscape of immunotherapy in
uterine cancer: A comprehensive review. Life. 2023;13:1502.
18. Corr B, et al. Endometrial cancer: Molecular classification
and future treatments. BMJ
Medicine. 2022;1(1):e000152.
19. FDA. FDA approves pembrolizumab with
chemotherapy for primary advanced or recurrent endometrial
carcinoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-primary-advanced-or-recurrent-endometrial-carcinoma.
Accessed June 2024.
20. Gov.uk. MHRA authorises monoclonal
antibody treatment, Jemperli, to be used with chemotherapy for
endometrial cancer. Available at https://www.gov.uk/government/news/mhra-authorises-monoclonal-antibody-treatment-jemperli-to-be-used-with-chemotherapy-for-endometrial-cancer.
Accessed June 2024.
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:
01 July 2024
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|