TIDMAZN
RNS Number : 2237G
AstraZeneca PLC
14 November 2022
14 November 2022 07:10 GMT
Enhertu recommended for approval in the EU by CHMP for patients
with previously treated HER2-positive advanced gastric cancer
Based on DESTINY-Gastric02 which showed AstraZeneca and Daiichi
Sankyo's Enhertu demonstrated clinically meaningful efficacy and
DESTINY-Gastric01 which showed improved overall survival compared
to chemotherapy
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab
deruxtecan) has been recommended for approval in the European Union
(EU) as monotherapy for the treatment of adult patients with
advanced HER2-positive gastric or gastroesophageal junction (GEJ)
adenocarcinoma who have received a prior trastuzumab-based
regimen.
Enhertu is a specifically engineered HER2-directed antibody drug
conjugate (ADC) being jointly developed and commercialised by
AstraZeneca and Daiichi Sankyo.
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency based its positive opinion on results
from the DESTINY-Gastric02 and the DESTINY-Gastric01 Phase II
trials.
In DESTINY-Gastric02, conducted in patients from North America
and Europe, updated results showed treatment with Enhertu resulted
in a confirmed objective response rate (ORR) of 41.8% as assessed
by independent central review (ICR). Median duration of response
(DoR) was 8.1 months and median overall survival (OS) was 12.1
months. Primary r esults from the DESTINY-Gastric02 Phase II trial
were presented at the 2021 European Society for Medical Oncology
(ESMO) Congress, with the updated data presented at ESMO
2022.(1)
In DESTINY-Gastric01, conducted in patients from Japan and South
Korea, updated results showed treatment with Enhertu resulted in an
ORR of 51.3% versus 14.3% with chemotherapy (irinotecan or
paclitaxel). Patients treated with Enhertu had a 40% reduction in
the risk of death versus patients treated with chemotherapy (based
on a hazard ratio of 0.60; 95% confidence interval : 0.42-0.86,
p=0.01 ) with a median OS of 12.5 months versus 8.9 months.
Additionally, confirmed ORR, a major efficacy outcome, was 42.0%
with Enhertu versus 12.5% with chemotherapy as assessed by ICR. The
primary analysis was published in The New England Journal of
Medicine , (2) with the updated data presented at the 2021 American
Society of Clinical Oncology Annual Meeting.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "G astric cancer is usually diagnosed in the
advanced stage in many European countries and patients face high
mortality rates. If approved, Enhertu would be the first
HER2-directed medicine for patients with advanced gastric cancer in
the European Union in more than a decade."
Ken Takeshita, Global Head, Oncology R&D, Daiichi Sankyo ,
Inc, said: "Enhertu is the first HER2-directed medicine to
demonstrate a significant improvement in overall survival compared
to chemotherapy in patients with gastric cancer following initial
treatment with a HER2-directed medicine in the advanced or
metastatic setting. The CHMP opinion recognises the high unmet need
in this patient population and brings us one step closer to
bringing this medicine to patients with gastric cancer in
Europe."
In both trials, the safety profiles observed in patients treated
with Enhertu were consistent with those seen in other trials of
Enhertu with no new safety signals identified.
Enhertu is approved in the US and several other countries for
locally advanced or metastatic HER2-positive gastric cancer.
Notes
HER2-positive gastric cancer
Gastric (stomach) cancer is the fifth most common cancer
worldwide and the fourth highest leading cause of cancer mortality,
with a five-year global survival rate of 5% to 10% for advanced or
metastatic disease.(3-5) Approximately one million new patients
were diagnosed with gastric cancer in 2020, with 768,000 deaths
reported globally.(6) In Europe, approximately 136,000 cases of
gastric cancer are diagnosed annually, and Eastern Europe has the
second highest incidence of gastric cancer worldwide after Eastern
Asia.(5-6) Gastric cancer is the sixth leading cause of cancer
death in Europe and is typically diagnosed in the advanced stage.
Even when diagnosed in earlier stages of the disease, the survival
rate remains modest.(5-7)
Approximately one in five gastric cancers are
HER2-positive.(8,9) HER2 is a tyrosine kinase receptor growth
promoting protein expressed on the surface of many types of tumours
including breast, gastric, lung and colorectal cancers.(8) HER2
overexpression may be associated with a specific HER2 gene
alteration known as HER2 amplification.(9)
Recommended first-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.(10) For patients with
metastatic gastric cancer that progresses following initial
treatment with a trastuzumab-based regimen, treatment options are
limited, and in many regions in the world there are no additional
HER2 directed medicines available.(2,11,12)
DESTINY-Gastric02
DESTINY-Gastric02 is an open-label, single-arm Phase II trial in
Western patients evaluating the efficacy and safety of Enhertu
(6.4mg/kg) in patients with HER2-positive metastatic and/or
unresectable gastric or GEJ adenocarcinoma with disease progression
on or after a trastuzumab-containing regimen.
The primary endpoint of DESTINY-Gastric02 is confirmed ORR based
on ICR. Secondary endpoints include progression-free survival
(PFS), OS, DoR and safety.
DESTINY-Gastric02 enrolled 79 patients at multiple sites in
North America and Europe. For more information about the trial,
visit ClinicalTrials.gov .
DESTINY-Gastric01
DESTINY-Gastric01 is a randomised, open-label Phase II trial
evaluating the efficacy and safety of Enhertu (6.4mg/kg) in
patients from Japan and South Korea with primarily HER2-positive
(defined as immunohistochemistry [IHC] 3+ or IHC 2+/in-situ
hybridisation [ISH]+) advanced gastric cancer or GEJ adenocarcinoma
whose tumours have progressed on two or more prior treatment
regimens including fluoropyrimidine (5-FU), platinum chemotherapy
and trastuzumab. Patients were randomised 2:1 to receive Enhertu or
physician's choice of chemotherapy (paclitaxel or irinotecan
monotherapy).
The primary endpoint of DESTINY-Gastric01 is ORR. Secondary
endpoints include OS, PFS, DoR, disease control rate and time to
treatment failure, as well as pharmacokinetic and safety
endpoints.
DESTINY-Gastric01 enrolled 187 patients at multiple sites in
Japan and South Korea. For more information about the trial, visit
ClinicalTrials.gov .
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo's
proprietary DXd ADC technology, Enhertu is the lead ADC in the
oncology portfolio of Daiichi Sankyo and the most advanced
programme in AstraZeneca's ADC scientific platform. Enhertu
consists of a HER2 monoclonal antibody attached to a topoisomerase
I inhibitor payload, an exatecan derivative, via a stable
tetrapeptide-based cleavable linker.
Enhertu (5.4mg/kg) is approved in more than 35 countries for the
treatment of adult patients with unresectable or metastatic
HER2-positive breast cancer who have received a (or one or more)
prior anti-HER2-based regimen either in the metastatic setting, or
in the neoadjuvant or adjuvant setting and have developed disease
recurrence during or within six months of completing therapy based
on the results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is approved in several countries for the
treatment of adult patients with unresectable or metastatic
HER2-positive breast cancer who have received two or more prior
anti-HER2-based regimens based on the results from the
DESTINY-Breast01 trial.
Enhertu (5.4mg/kg) is approved in Brazil and the US for the
treatment of adult patients with unresectable or metastatic
HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a
prior chemotherapy in the metastatic setting or developed disease
recurrence during or within six months of completing adjuvant
chemotherapy based on the results from the DESTINY-Breast04
trial.
Enhertu (5.4mg/kg) is approved under accelerated approval in the
US for the treatment of adult patients with unresectable or
metastatic non-small cell lung cancer whose tumours have activating
HER2 (ERBB2) mutations, as detected by an FDA-approved test, and
who have received a prior systemic therapy, based on the results of
the DESTINY-Lung02 trial. Continued approval for this indication
may be contingent upon verification and description of clinical
benefit in a confirmatory trial.
Enhertu (6.4mg/kg) is approved in several countries for the
treatment of adult patients with locally advanced or metastatic
HER2-positive gastric or GEJ who have received a prior
trastuzumab-based regimen based on the results from the
DESTINY-Gastric01 trial.
Enhertu development programme
A comprehensive development programme is underway globally,
evaluating the efficacy and safety of Enhertu monotherapy across
multiple HER2-targetable cancers, including breast, gastric, lung
and colorectal cancers. Trials in combination with other anticancer
treatments, such as immunotherapy, are also underway.
Regulatory applications for Enhertu in breast and gastric cancer
are currently under review in several other countries based on the
DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04,
DESTINY-Gastric01 and DESTINY-Gastric02 trials, respectively.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as
Daiichi Sankyo] and AstraZeneca entered into a global collaboration
to jointly develop and commercialise Enhertu (a HER2-directed ADC)
in March 2019 , and datopotamab deruxtecan (DS-1062; a
TROP2-directed ADC) in July 2020 , except in Japan where Daiichi
Sankyo maintains exclusive rights. Daiichi Sankyo is responsible
for the manufacturing and supply of Enhertu and datopotamab
deruxtecan.
AstraZeneca in gastrointestinal cancers
AstraZeneca has a broad development programme for the treatment
of gastrointestinal (GI) cancers across several medicines and a
variety of tumour types and stages of disease. In 2020, GI cancers
collectively represented approximately 5.1 million new cancer cases
leading to approximately 3.6 million deaths.(13)
Within this programme, the Company is committed to improving
outcomes in gastric, liver, biliary tract, oesophageal, pancreatic
and colorectal cancers.
Enhertu , a HER2-directed antibody drug conjugate, is approved
in the US and several other countries for HER2-positive advanced
gastric cancer and is being assessed in colorectal cancer. Enhertu
is jointly developed and commercialised by AstraZeneca and Daiichi
Sankyo.
Imfinzi (durvalumab) is approved in the US and several other
countries in combination with chemotherapy (gemcitabine plus
cisplatin) for advanced biliary tract cancer and in the US in
combination with Imjudo (tremelimumab) in unresectable
hepatocellular carcinoma. Imfinzi is being assessed in
combinations, including with Imjudo, in liver, oesophageal and
gastric cancers in an extensive development programme spanning
early to late-stage disease across settings.
Lynparza (olaparib), a first-in-class PARP inhibitor, is
approved in the US and several other countries for the treatment of
BRCA-mutated metastatic pancreatic cancer. Lynparza is developed
and commercialised in collaboration with MSD (Merck & Co., Inc.
inside the US and Canada).
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 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 .
Contacts
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References
1. Updated analysis of DESTINY-Gastric02. Available at: https://oncologypro.esmo.org/meeting-resources/esmo-congress/updated-analysis-of-destiny-gastric02-a-phase-ii-single-arm-trial-of-trastuzumab-deruxtecan-t-dxd-in-western-patients-pts-with-her2-positive . Accessed November 2022.
2. Shitara K, et al. Trastuzumab Deruxtecan in Previously
Treated HER2-Positive Gastric Cancer. N Engl J Med 2020;
382:2419-2430.
3. Casamayor M, et al. Targeted literature review of the global burden of gastric cancer. Ecancermedicalscience. 2018; 12:883;12:883.
4. SEER Cancer Stat Facts: Stomach Cancer. Available at:
https://seer.cancer.gov/statfacts/html/stomach.html . Accessed
November 2022.
5. Sung. H et al. Global cancer statistics 2020: GLOBOCAN
estimates of incidence and mortality worldwide for 36 cancers in
185 countries. CA Cancer J Clin. 2021; 10.3322/caac.21660.
6. WHO. International Agency of Cancer Research. Cancer Today.
Stomach Incidence. 2020. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf
. Accessed November 2022.
7. Cancer Research UK. Stomach Cancer Survival Statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/stomach-cancer/survival#heading-Zero . Accessed November 2022.
8. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2
(HER2) in Cancers: Overexpression and Therapeutic Implications. Mol
Biol Int. 2014; 2014:852748.
9. Abrahao-Machado LF, et al. HER2 testing in gastric cancer: An
update. World J Gastroenterol. 2016; 22(19):4619-4625.
10. Orditura M, et al. "Treatment of gastric cancer." World
Journal of Gastroenterology: WJG 20.7 (2014): 1635.
11. Thuss-Patience PC, et al. Trastuzumab emtansine versus
taxane use for previously treated HER2-positive locally advanced or
metastatic gastric or gastro-oesophageal junction adenocarcinoma
(GATSBY): an international randomised, open-label, adaptive, phase
2/3 study. Lancet Oncol. 2017; 18(5):640-653.
12. Satoh T, et al. Lapatinib Plus Paclitaxel Versus Paclitaxel
Alone in the Second-Line Treatment of HER2-Amplified Advanced
Gastric Cancer in Asian Populations: TyTAN-A Randomized, Phase III
Study. J Clin Oncol.2014; 32(19):2039 -- 2049.
13. WHO. World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed November 2022.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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