REG - AstraZeneca PLC - Lynparza + Imfinzi met endpoint in ovarian cancer

AstraZenecaAnnouncement

05/04/2023 07:15

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RNS Number : 4488V  AstraZeneca PLC  05 April 2023

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
(https://clinicaltrials.gov/ct2/show/NCT03737643) .

 

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
(https://www.astrazeneca.com/) and follow the Company on Twitter @AstraZeneca
(https://twitter.com/AstraZeneca?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor)
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Contacts

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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
(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.
(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

 

 

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