REG - AstraZeneca PLC - Imfinzi + Lynparza prolonged PFS in endometrial ca

AstraZenecaAnnouncement

26/05/2023 07:00

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RNS Number : 7373A  AstraZeneca PLC  26 May 2023

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
(https://clinicaltrials.gov/ct2/show/NCT04269200) .

 

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 (https://www.astrazeneca.com) and follow the
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Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
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References

1.   World Cancer Research Fund International. Endometrial Cancer
Statistics. Available at
https://www.wcrf.org/cancer-trends/endometrial-cancer-statistics/
(https://www.wcrf.org/cancer-trends/endometrial-cancer-statistics/#:~:text=There%20were%20more%20than%20417%2C000,shown%20in%20the%20tables%20below.)
. 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
(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=900)
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
(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
(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.
(https://www.cancer.org/cancer/types/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

 

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