TIDMAZN
RNS Number : 9767A
AstraZeneca PLC
27 January 2020
27 January 2020 07:00 GMT
Phase II DESTINY-Gastric01 trial of Enhertu versus
chemotherapy met primary endpoint
Trial met primary endpoint of objective response rate and key
secondary
endpoint of overall survival in patients with previously treated
HER2-positive metastatic gastric cancer
High-level results from the positive registrational Phase II
trial DESTINY-Gastric01 showed AstraZeneca's and Daiichi Sankyo
Company, Limited (Daiichi Sankyo)'s Enhertu (trastuzumab
deruxtecan), achieved a statistically significant and clinically
meaningful improvement in objective response rate (ORR) and overall
survival (OS) in patients with HER2-positive unresectable or
metastatic gastric or gastroesophageal junction cancer that had
progressed following two or more treatment regimens including
trastuzumab and chemotherapy.
The trial met its primary endpoint of an improvement in ORR, as
assessed by an independent review committee, in patients treated
with Enhertu compared to investigator's choice of chemotherapy
(irinotecan or paclitaxel monotherapy). Enhertu also showed a
statistically significant and clinically meaningful improvement in
OS, a key secondary endpoint.
José Baselga, Executive Vice President, Oncology R&D, said:
"Gastric cancer is usually diagnosed in the advanced stage and
patients face markedly high mortality rates, making the need for
new therapies especially urgent. Given the previous results seen in
our HER2-positive development programme and now in HER2-positive
metastatic gastric cancer, we believe this antibody drug conjugate
has the potential to redefine the treatment of patients with
HER2-expressing cancers."
Gilles Gallant, Senior Vice President, Global Head, Oncology
Development, Oncology R&D, Daiichi Sankyo, said: "We are
excited to report positive top-line results from this trial. Our
development plan remains on track in gastric cancer, including an
initial regulatory application in Japan where gastric cancer is
highly prevalent, and where SAKIGAKE designation has been granted
for this indication. We are strongly committed to bringing this
therapy as rapidly as possible to patients in need."
The overall safety and tolerability profile of Enhertu in
DESTINY-Gastric01 was consistent with that seen in the published
Phase I trial in which the most common adverse events (>=30
percent, any grade) were haematologic and gastrointestinal
including neutrophil count decrease, anaemia, nausea and decreased
appetite. There were cases of treatment-related interstitial lung
disease (ILD) and pneumonitis, the majority of which were Grade 1
and 2 with two Grade 3 and one Grade 4. No ILD-related deaths
(Grade 5) occurred in gastric patients in the Phase I trial or in
the DESTINY-Gastric01 trial.
These results confirm activity seen in the non-randomised Phase
I trial of Enhertu in patients with HER2-positive advanced gastric
cancer published in The Lancet Oncology.(1) Data from
DESTINY-Gastric01 will be presented at a forthcoming medical
meeting.
In addition to the planned discussion with the Japan Ministry of
Health, Labour and Welfare (MHLW), both companies plan to discuss
the data with other health authorities. Enhertu recently received
Accelerated Approval in the US for HER2-positive unresectable or
metastatic breast cancer following two or more prior anti-HER2
based treatment regimens and additional global regulatory
submissions in HER2-positive metastatic breast cancer are
underway.
Enhertu is being jointly developed and commercialised worldwide
with AstraZeneca except in Japan where Daiichi Sankyo maintains
exclusive rights.
HER2
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours including
gastric, breast and lung cancers. HER2 overexpression is often
associated with aggressive disease and poorer prognosis.(2) When a
patient is diagnosed with gastric cancer, guidelines recommend
evaluating HER2-expression levels by an immunohistochemistry (IHC)
test.(3) A finding of IHC 3+ is considered positive. A result of
IHC 2+ is considered equivocal, in which case an additional testing
method of in situ hybridisation (ISH) is recommended to confirm
HER2 status.
Gastric cancer
Gastric (stomach) cancer is the fifth most common cancer
worldwide and the third leading cause of cancer mortality; there
were approximately one million new cases reported in 2018 and
783,000 deaths.(4) Incidence rates for gastric cancer are markedly
higher in eastern Asia, where approximately half of all cases
occur.(4) South Korea and Japan have the first and third highest
incidence rates of gastric cancer worldwide, respectively; in 2018,
the age-standardised rate in Japan was 27.5 per 100,000 and in
South Korea it was 39.6 per 100,000.(5)
Approximately one in five gastric cancers are HER2 positive.(6)
Gastric cancer is usually diagnosed in the advanced stage, but even
when diagnosed in earlier stages of the disease the survival rate
remains modest.(7) Recommended 1st-line treatment for HER2-positive
advanced or metastatic gastric cancer is combination chemotherapy
plus trastuzumab, an anti-HER2 medicine, which has been shown to
improve survival outcomes when added to chemotherapy.(8) For
gastric cancer that progresses on trastuzumab, there are no other
approved HER2-targeting medicines and subsequent treatment options
are limited.(9)
DESTINY-Gastric01
DESTINY-Gastric01 is a registrational Phase II, open-label,
multi-centre trial assessing the safety and efficacy of Enhertu in
189 patients from Japan and South Korea with HER2-expressing
advanced gastric cancer or gastroesophageal junction adenocarcinoma
(defined as IHC3+ or IHC2+/ISH+) who have progressed on two or more
prior treatment regimens including fluoropyrimidine (5-FU) and
platinum chemotherapy and trastuzumab. Patients were randomised 2:1
to receive Enhertu or investigator's choice of chemotherapy
(paclitaxel or irinotecan monotherapy). Patients were treated with
Enhertu 6.4mg/kg once every three weeks or chemotherapy given on
the same schedule. The primary endpoint of the trial is ORR.
Secondary endpoints include OS, progression-free survival, duration
of response, disease control rate and time to treatment failure as
well as pharmacokinetic and safety endpoints.
Enhertu
Enhertu (fam-trastuzumab deruxtecan-nxki in the US only;
trastuzumab deruxtecan outside the US) is a HER2-directed antibody
drug conjugate (ADC) and is the lead product in the ADC Franchise
of the Daiichi Sankyo Cancer Enterprise and the most advanced
programme in AstraZeneca's ADC scientific platform. ADCs are
targeted cancer medicines that deliver cytotoxic chemotherapy
("payload") to cancer cells via a linker attached to a monoclonal
antibody that binds to a specific target expressed on cancer
cells.
Enhertu clinical development
A comprehensive development programme is underway globally with
five registrational trials in HER2-expressing metastatic breast and
gastric cancers including a trial in patients with metastatic
breast cancer and low levels of HER2 expression. Phase II trials
are underway for HER2-expressing advanced colorectal cancer, as
well as metastatic non-squamous HER2-overexpressing or HER2-mutated
non-small cell lung cancer. Trials in combination with other
anticancer treatments, such as immunotherapy, are also
underway.
Collaboration between AstraZeneca and Daiichi Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a
global collaboration to jointly develop and commercialise Enhertu
worldwide, except in Japan where Daiichi Sankyo maintains exclusive
rights. Daiichi Sankyo is solely responsible for manufacturing and
supply.
AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients' lives and the Company's future. With at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, the
Company is committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - 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/NYSE: 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 and Metabolism, and Respiratory.
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.
Media Relations
Gonzalo Viña +44 203 749 5916
Rob Skelding Oncology +44 203 749 5821
Rebecca Einhorn Oncology +1 301 518 4122
Matt Kent BioPharmaceuticals +44 203 749 5906
Angela Fiorin BioPharmaceuticals +44 1223 344 690
Jennifer Hursit Other +44 203 749 5762
Christina Malmberg Hägerstrand Sweden +46 8 552 53 106
Michele Meixell US +1 302 885 2677
Investor Relations
Thomas Kudsk Larsen +44 203 749 5712
Henry Wheeler Oncology +44 203 749 5797
BioPharmaceuticals
Christer Gruvris (Cardiovascular, Metabolism) +44 203 749 5711
BioPharmaceuticals (Renal) Environmental, Social and
Nick Stone Governance +44 203 749 5716
Josie Afolabi BioPharmaceuticals (Respiratory) +44 203 749 5631
Tom Waldron Other medicines +44 7385 033 717
Finance
Craig Marks Fixed income +44 7881 615 764
Corporate access
Jennifer Kretzmann Retail investors +44 203 749 5824
US toll-free +1 866 381 72 77
References
1. Shitara K et al. Lancet Oncol. 2019; S1470-2045 (19):30088-9.
2. Iqbal and Iqbal. Mol Biol Int. 2014; 2014: 852748.
3. NCCN Guidelines(R) Gastric Cancer. Version 4.2019. December 20, 2019: GAST-B 3.
4. Bray F et al. GLOBOCAN CA CANCER J CLIN 2018;68:394-424.
5. World Cancer Research Fund International. Stomach Cancer
Statistics. 2018. Accessed 25 January 2020:
https://www.wcrf.org/dietandcancer/cancer-trends/stomach-cancer-statistics.
6. American Cancer Society. Tests for Stomach Cancer. 2017. Accessed 25 January 2020: https://www.cancer.org/cancer/stomach-cancer/treating/targeted-therapies.html.
7. Curea et al. Cancer Biotherapy & Radiopharmaceuticals. 2017;32 (10): Review.
8. NCCN Guidelines(R) Gastric Cancer. Version 4.2019. December 20, 2019: MS-22.
9. NCCN Guidelines(R) Gastric Cancer. Version 4.2019. December 20, 2019: MS-36.
Adrian Kemp
Company Secretary
AstraZeneca PLC
This information is provided by RNS, the news service of the
London Stock Exchange. RNS is approved by the Financial Conduct
Authority to act as a Primary Information Provider in the United
Kingdom. Terms and conditions relating to the use and distribution
of this information may apply. For further information, please
contact rns@lseg.com or visit www.rns.com.
END
MSCPPUUUGUPUUQM
(END) Dow Jones Newswires
January 27, 2020 02:00 ET (07:00 GMT)
Grafico Azioni Astrazeneca (LSE:AZN)
Storico
Da Mar 2024 a Apr 2024
Grafico Azioni Astrazeneca (LSE:AZN)
Storico
Da Apr 2023 a Apr 2024
