REG - AstraZeneca PLC - Enhertu recommended in EU for HER2-mutant NSCLC

AstraZenecaAnnouncement

15/09/2023 15:00

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RNS Number : 6519M  AstraZeneca PLC  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 cancer

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 disease

 

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
immunotherapy.

 

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
(https://www.astrazeneca.com/media-centre/press-releases/2023/enhertu-demonstrated-strong-and-durable-tumour-responses-in-previously-treated-her2-mutant-advanced-lung-cancer-in-the-destiny-lung02-phase-ii-trial.html)
Phase II trial, which were presented at the IASLC 2023 World Conference on
Lung Cancer and simultaneously published in the Journal of Clinical Oncology
(https://ascopubs.org/doi/full/10.1200/JCO.23.01361) .

 

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 December 2022.

 

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 identified.

 

Notes

 

HER2m NSCLC

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

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 6.4mg/kg (n=50).

 

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 (https://clinicaltrials.gov/ct2/show/NCT04644237) .

 

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 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
DESTINY-Breast04 trial.

 

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 DESTINY-Gastric02 trials.

 

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 underway.

 

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
(https://www.astrazeneca.com/media-centre/press-releases/2019/astrazeneca-and-daiichi-sankyo-enter-collaboration-for-novel-her-2-targeting-antibody-drug-conjugate.html)
, and datopotamab deruxtecan (a TROP2-directed ADC) in July 2020
(https://www.astrazeneca.com/media-centre/press-releases/2020/astrazeneca-and-daiichi-sankyo-enter-collaboration-to-develop-and-commercialise-new-antibody-drug-conjugate.html)
, 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 beyond treatment.

 

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

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   WHO. International Agency of Cancer Research. Cancer Today. 2020.
Available at: https://gco.iarc.fr/today/home (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
(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
(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. 2018;24(11):2594-2604.

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. 2021;6(5):100260.

6.   Pillai RN, et al. HER2 mutations in lung adenocarcinomas: A report from
the Lung Cancer Mutation Consortium. Cancer. 2017;123:4099-105.

7.   Offin M, et al. Frequency and Outcomes of Brain Metastases in Patients
With HER2-Mutant Lung Cancers. Cancer. 2019;125(24):4380-4387.

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; 127(7):428-431.

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. 2020;12:1758835920937612.

11.  Ren S, et al. Corrigendum to 'Consensus for HER2 Alterations Testing in
Non-small Cell Lung Cancer'. ESMO Open. 2022;7(3):100482.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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