RNS Number : 6519M
15 September 2023
15 September 2023
Enhertu recommended for approval in the EU by CHMP for
patients with HER2-mutant advanced non-small cell lung
Recommendation based on DESTINY-Lung02 trial results which
showed AstraZeneca and Daiichi Sankyo's Enhertu achieved strong and
durable tumour responses in previously treated HER2-mutant
Enhertu showed a confirmed objective response rate of 49% and
median duration of response of 16.8 months
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 non-small cell lung cancer (NSCLC) whose tumours have an
activating HER2 (ERBB2) mutation and who require systemic therapy
following platinum-based chemotherapy with or without
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 the primary
results from the DESTINY-Lung02 Phase II trial, which were
presented at the IASLC 2023 World Conference on Lung Cancer and
simultaneously published in the Journal of Clinical Oncology.
In the trial, Enhertu (5.4mg/kg) demonstrated a confirmed
objective response rate (ORR) of 49.0% (95% confidence interval
[CI] 39.0-59.1) and a disease control rate (DCR) of 93.1% (95% CI
86.4-97.2), as assessed by blinded independent central review
(BICR), in patients with previously treated advanced or metastatic
HER2-mutant (HER2m) NSCLC. One (1.0%) complete response (CR) and 49
(48.0%) partial responses (PR) were observed. The median duration
of response (DoR) was 16.8 months (95% CI 6.4-not estimated [NE]).
Median follow-up was 11.5 months at time of data cut-off of 23
Susan Galbraith , Executive Vice President, Oncology R&D,
AstraZeneca , said: "HER2-mutant non-small cell lung cancer is an
aggressive form of lung cancer that often affects younger patients
and has a poor prognosis, with limited approved therapies. This
milestone recognises the unmet need in the European Union and if
approved, Enhertu will provide the first targeted treatment option
for these patients."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said:
"Enhertu is the first therapy to demonstrate a strong and durable
tumour response in patients with previously treated HER2-mutant
advanced non-small cell lung cancer, validating HER2 as an
actionable target in lung cancer and supporting the potential to
provide a much-needed option for these patients. This CHMP opinion
is a positive step forward in advancing this HER2-directed antibody
drug conjugate for these patients and we look forward to the
European Commission decision."
The safety profile of Enhertu in the DESTINY-Lung02 trial was
consistent with previous clinical trials with no new safety signals
Lung cancer is the second most common form of cancer globally
with more than two million cases diagnosed in 2020.(1) In Europe,
lung cancer is the third most commonly diagnosed cancer with more
than 477,000 cases diagnosed in 2020.(2) Lung cancer is also the
leading cause of cancer-related deaths in Europe, with nearly
400,000 deaths reported in 2020.(2) Prognosis is particularly poor
for patients with metastatic NSCLC as only approximately 9% will
live beyond five years after diagnosis.(3)
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including lung,
breast, gastric and colorectal cancers. Certain HER2 (ERBB2) gene
alterations (called HER2 mutations) have been identified in
patients with non-squamous NSCLC as a distinct molecular target,
and occur in approximately 2-4% of patients with this type of lung
cancer.(4,5) While HER2 gene mutations can occur in a range of
patients, they are more commonly found in patients with NSCLC who
are younger, female and have never smoked.(6) HER2 gene mutations
have been independently associated with cancer cell growth and poor
prognosis, with an increased incidence of brain metastases.(7)
Next-generation sequencing has been utilised in the identification
of HER2 (ERBB2) mutations.(8,9)
Although the role of anti-HER2 treatment is well established in
breast and gastric cancers, there were no approved HER2-directed
therapies in NSCLC prior to the approvals of Enhertu by the Israel
Ministry of Health (MOH) Pharmaceutical Division, the Japan
Ministry of Health, Labour and Welfare and the accelerated US Food
and Drug Administration (FDA) approval of Enhertu in unresectable
or metastatic HER2m NSCLC.(10,11)
DESTINY-Lung02 is a global, randomised Phase II trial evaluating
the safety and efficacy of Enhertu in patients with HER2m advanced
or metastatic NSCLC with disease recurrence or progression during
or after at least one regimen of prior anticancer therapy that must
have contained a platinum-based chemotherapy. Patients were
randomised 2:1 to receive Enhertu 5.4mg/kg (n=102) or Enhertu
The primary endpoint of the trial is confirmed ORR as assessed
by BICR. Secondary endpoints include confirmed DCR, DoR and PFS
assessed by investigator and BICR, OS and safety.
DESTINY-Lung02 enrolled 152 patients at multiple sites,
including Asia, Europe and North America. For more information
about the trial, visit ClinicalTrials.gov .
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 50 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 more than 40 countries
worldwide 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 systemic therapy in the metastatic setting or
developed disease recurrence during or within six months of
completing adjuvant chemotherapy based on the results from the
Enhertu (5.4mg/kg) is approved in Israel, Japan and under
accelerated approval in the US for the treatment of adult patients
with unresectable or metastatic NSCLC whose tumours have activating
HER2 (ERBB2) mutations, as detected by a locally or regionally
approved test, and who have received a prior systemic therapy based
on the results from the DESTINY-Lung02 trial. Continued approval
for this indication in the US may be contingent upon verification
and description of clinical benefit in a confirmatory trial.
Enhertu (6.4mg/kg) is approved in more than 30 countries for the
treatment of adult patients with locally advanced or metastatic
HER2-positive gastric or gastroesophageal junction (GEJ)
adenocarcinoma who have received a prior trastuzumab-based regimen
based on the results from the DESTINY-Gastric01 and/or
Enhertu development programme
A comprehensive clinical development programme is underway
globally, evaluating the efficacy and safety of Enhertu monotherapy
across multiple HER2-targetable cancers. Trials in combination with
other anticancer treatments, such as immunotherapy, are also
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 (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 lung cancer
AstraZeneca is working to bring patients with lung cancer closer
to cure through the detection and treatment of early-stage disease,
while also pushing the boundaries of science to improve outcomes in
the resistant and advanced settings. By defining new therapeutic
targets and investigating innovative approaches, the Company aims
to match medicines to the patients who can benefit most.
The Company's comprehensive portfolio includes leading lung
cancer medicines and the next wave of innovations, including
Tagrisso ( osimertinib ) and Iressa (gefitinib); Imfinzi
(durvalumab) and Imjudo (tremelimumab); Enhertu and datopotamab
deruxtecan in collaboration with Daiichi Sankyo; Orpathys (
savolitinib ) in collaboration with HUTCHMED; as well as a pipeline
of potential new medicines and combinations across diverse
mechanisms of action.
AstraZeneca is a founding member of the Lung Ambition Alliance,
a global coalition working to accelerate innovation and deliver
meaningful improvements for people with lung cancer, including and
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 (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 social media @ AstraZeneca .
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1. WHO. International Agency of Cancer Research. Cancer Today. 2020. Available at: https://gco.iarc.fr/today/home . Accessed September 2023.
2. WHO. International Agency of Cancer Research. Europe. 2020. Available at: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf . Accessed September 2023.
3. American Cancer Society. Lung Cancer Survival Rates. Available at: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html . Accessed September 2023.
4. Liu S, et al. Targeting HER2 Aberrations in Non-Small Cell
Lung Cancer with Osimertinib. Clin Cancer Res.
5. Riudavets M, et al. Targeting HER2 in non-small-cell lung
cancer (NSCLC): a glimpse of hope? An updated review on therapeutic
strategies in NSCLC harbouring HER2 alterations. ESMO Open.
6. Pillai RN, et al. HER2 mutations in lung adenocarcinomas: A
report from the Lung Cancer Mutation Consortium. Cancer.
7. Offin M, et al. Frequency and Outcomes of Brain Metastases in
Patients With HER2-Mutant Lung Cancers. Cancer.
8. Hechtman, J, et al. The Past, Present, and Future of HER2
(ERBB2) in Cancer: Approaches to Molecular Testing and an Evolving
Role in Targeted Therapy. Cancer Cytopathol. 2019;
9. Gulilat, M, et al. Targeted next generation sequencing as a
tool for precision medicine. BMC Med Genomics. 2019 ;12(1):81.
10. Zhou J, et al. Efficacy of PD-1/PD-L1 blockade monotherapy
in clinical trials. Ther Adv Med Oncol.
11. Ren S, et al. Corrigendum to 'Consensus for HER2 Alterations
Testing in Non-small Cell Lung Cancer'. ESMO Open.
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September 15, 2023 10:00 ET (14:00 GMT)
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