REG - AstraZeneca PLC - Imfinzi approved in the US for endometrial cancer

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17/06/2024 07:15

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RNS Number : 5955S  AstraZeneca PLC  17 June 2024

17 June 2024

 

Imfinzi plus chemotherapy approved in the US for

mismatch repair deficient advanced or recurrent endometrial cancer

Approval based on DUO-E trial results, which showed Imfinzi reduced the

risk of disease progression or death by 58% vs. chemotherapy

 

AstraZeneca's Imfinzi (durvalumab) in combination with carboplatin and
paclitaxel followed by Imfinzi monotherapy has been approved in the US as
treatment for adult patients with primary advanced or recurrent endometrial
cancer that is mismatch repair deficient (dMMR).(1)

 

The approval by the Food and Drug Administration (FDA) was based on the
results of a prespecified exploratory subgroup analysis by MMR status in the
DUO-E Phase III
(https://www.astrazeneca.com/media-centre/press-releases/2023/imfinzi-plus-lynparza-reduced-risk-disease-progression-death-45-percent-vs-chemotherapy-advanced-recurrent-endometrial-cancer.html#!)
trial. Results from DUO-E were published in the Journal of Clinical Oncology
(https://ascopubs.org/doi/full/10.1200/JCO.23.02132) .

 

In the trial, Imfinzi plus carboplatin and paclitaxel followed by Imfinzi
monotherapy (Imfinzi arm) reduced the risk of disease progression or death by
58% in patients with dMMR endometrial cancer versus chemotherapy alone (hazard
ratio 0.42; 95% confidence interval 0.22-0.80).(2)

 

In the US, endometrial cancer is the fourth most common cancer in women, with
more than 66,000 patients diagnosed and almost 12,000 deaths in 2022.(3,4)
Patients diagnosed at an early stage of disease have a five-year survival rate
of approximately 80-90%, but there is a significant need for new treatment
options for people with advanced disease, where the survival rate falls to
less than 20%.(5,6)

 

Shannon N. Westin, Professor of Gynecologic Oncology and Reproductive Medicine
at The University of Texas MD Anderson Cancer Center, and principal
investigator of the trial, said, "With the incidence and mortality of
endometrial cancer expected to continue to increase significantly in the
coming decades, it is more important than ever that we bring new treatment
options to patients at the earliest possible moment in their care. This
approval underlines clear evidence that durvalumab plus chemotherapy followed
by durvalumab monotherapy delivers important clinical benefits for patients
with mismatch repair deficient endometrial cancer."

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "There have been limited advances in the treatment of
endometrial cancer in the last few decades, and continued innovation is
critical as the burden of this cancer is expected to grow in the future.
Immunotherapy in combination with chemotherapy is emerging as a new standard
of care in this setting, and the approval of Imfinzi offers an important new
option for patients with mismatch repair deficient disease."

 

The safety and tolerability profile of the Imfinzi and chemotherapy regimen
was generally manageable, well tolerated and broadly consistent with prior
clinical trials with no new safety signals.(1,2)

 

The Lynparza (olaparib) and Imfinzi arm, which investigated Imfinzi plus
chemotherapy followed by Imfinzi plus Lynparza as maintenance therapy, also
met the primary endpoint of progression-free survival (PFS). The trial
continues to assess OS as a key secondary endpoint for both arms. Regulatory
applications for both Imfinzi as well as Imfinzi and Lynparza regimens are
currently under review in the EU, Japan and several other countries based on
the DUO-E results.

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.(7-10) It is the sixth most common cancer in women worldwide.(11,12)
Incidence and mortality of endometrial cancer are expected to increase by
approximately 61% and 87% respectively (from 420,400 cases and 97,700 deaths
in 2022 to 676,300 cases and 183,100 deaths) in 2050.(13)

 

The majority of patients with endometrial cancer are diagnosed at an early
stage of disease, where the cancer is confined to the uterus.(9,10) They are
typically treated with surgery and/or radiation, and the five-year survival
rate is high (approximately 80-90%).(5,6) Patients with advanced disease
(Stage III-IV) usually have a much poorer prognosis, with the five-year
survival rate falling to less than 20%.(5,6) 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 with this type of cancer.(6,14,15,16) There remains a
high unmet need for treatments for the remaining 70-80% of endometrial cancer
patients with pMMR disease.(15,16)

 

DUO-E

The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised,
double-blind, placebo-controlled, multicentre Phase III trial of 1(st)-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 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
(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.

 

In addition to its indications in unresectable, Stage III NSCLC and ES-SCLC,
Imfinzi is currently approved in a number of countries in combination with a
short course of tremelimumab (Imjudo) and chemotherapy for the treatment of
metastatic NSCLC.

 

Imfinzi is also approved in a number of countries in combination with
chemotherapy 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.

 

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 (https://www.astrazeneca.com) and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca/) .

Contacts

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.

 

References

1.   Imfinzi (durvalumab) US prescribing information; Jun 2024.

2.   Shannon N. Westin 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. JCO 42,
283-299(2024).

3.   World Health Organization. IARC. Absolute numbers, Incidence, Females,
in 2022. United States of America. Available at:
https://gco.iarc.fr/today/en/dataviz/pie?mode=cancer&cancers=24&sexes=2&group_populations=1&populations=840
(https://gco.iarc.fr/today/en/dataviz/pie?mode=cancer&cancers=24&sexes=2&group_populations=1&populations=840)
. Accessed Jun 2024.

4.   World Health Organization. IARC. Corpus Uteri. Estimated numbers from
2022 to 2050, United States, Females, age  0-85+ . Available at:
https://gco.iarc.who.int/tomorrow/en/dataviz/trends?multiple_populations=1&cancers=24&populations=840
(https://gco.iarc.who.int/tomorrow/en/dataviz/trends?multiple_populations=1&cancers=24&populations=840)
. Accessed Jun 2024.

5.   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 Jan
9;23(1):31.

6.   Haj Hamoud B, et al. The Evolving Landscape Of Immunotherapy In Uterine
Cancer: A Comprehensive Review. Life. 2023;13(7):1502.

7.   Dork T, et al. Genetic Susceptibility to Endometrial Cancer: Risk
Factors and Clinical Management. Cancers (Basel). 2020;12(9):2407.

8.   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/endometrial-cancer/about/what-is-endometrial-cancer.html)
. Accessed Jun 2024.

9.   Oakin A, et al. ESMO Guidelines. Endometrial Cancer: ESMO Clinical
Practice Guidelines for Diagnosis, Treatment and Follow-Up. Ann Oncol.
2022;33(9):860-877.

10.  Cancer.Net. Uterine Cancer: Statistics. Available at:
https://www.cancer.net/cancer-types/uterine-cancer/statistics. Accessed Jun
2024.

11.  World Cancer Research Fund International. Endometrial Cancer Statistics.
Available at
https://www.wcrf.org/cancer-trends/endometrial-cancer-statistics/. Accessed
Jun 2024.

12.  World Health Organisation. IARC. Corpus Uteri. Absolute numbers,
Incidence, Females in 2022. Available at:
https://gco.iarc.who.int/today/en/dataviz/pie?mode=cancer&group_populations=1&populations=900&sexes=2
(https://gco.iarc.who.int/today/en/dataviz/pie?mode=cancer&group_populations=1&populations=900&sexes=2)
. Accessed Jun 2024.

13.  World Health Organization. IARC. Corpus Uteri. Estimated Numbers From
2022 To 2050, Females, Age  0-85+  World. Available at
https://gco.iarc.who.int/tomorrow/en/dataviz/trends?multiple_populations=1&cancers=24
(https://gco.iarc.who.int/tomorrow/en/dataviz/trends?multiple_populations=1&cancers=24)
. Accessed Jun 2024.

14.  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
(https://www.gov.uk/government/news/mhra-authorises-monoclonal-antibody-treatment-jemperli-to-be-used-with-chemotherapy-for-endometrial-cancer)
. Accessed Jun 2024.

15.  Yang Y, et al. Molecular Subtypes Of Endometrial Cancer: Implications
For Adjuvant Treatment Strategies. International Journal of Gynecology &
Obstetrics. 2023;00:1-24.

16.  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.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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