REG - AstraZeneca PLC - Enhertu granted Priority Review for HER2m NSCLC

AstraZenecaAnnouncement

19/04/2022 07:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20220419:nRSS5055Ia&default-theme=true

RNS Number : 5055I  AstraZeneca PLC  19 April 2022

19 April 2022 07:00 BST

 

Enhertu( )granted Priority Review in the US for patients with previously
treated HER2-mutant metastatic non-small cell lung cancer

 

Based on pivotal DESTINY-Lung01 results showing AstraZeneca and Daiichi
Sankyo's Enhertu demonstrated a 54.9% tumour response rate

 

If approved, Enhertu to provide patients with a much-needed targeted therapy
option

 

AstraZeneca and Daiichi Sankyo have received notification of acceptance of the
supplemental Biologics License Application (sBLA) of Enhertu (trastuzumab
deruxtecan) for the treatment of adult patients in the US with unresectable or
metastatic non-small cell lung cancer (NSCLC) whose tumours have a HER2
(ERBB2) mutation and who have received a prior systemic therapy. The
application has also been granted Priority Review.

 

Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly
developed by AstraZeneca and Daiichi Sankyo.

 

The Food and Drug Administration (FDA) grants Priority Review to applications
for medicines that, if approved, would offer significant improvements over
available options by demonstrating safety or efficacy improvements, preventing
serious conditions, or enhancing patient compliance.(1) The Prescription Drug
User Fee Act (PDUFA) date, the FDA action date for their regulatory decision,
is during the third quarter of 2022. The Priority Review follows Breakthrough
Therapy Designation
(https://www.astrazeneca.com/media-centre/press-releases/2020/enhertu-granted-breakthrough-therapy-designation-in-the-us-for-her2-mutant-metastatic-non-small-cell-lung-cancer.html)
granted by the FDA for Enhertu in this cancer type in May 2020.

 

Lung cancer is the second most common form of cancer globally, with more than
two million new cases diagnosed in 2020.(2) For patients with metastatic
NSCLC, prognosis is particularly poor, as only approximately 8% will live
beyond five years after diagnosis.(3) There are currently no HER2-directed
therapies approved specifically for the treatment of HER2-mutant NSCLC,(4)
which occurs in approximately 2-4% of patients with non-squamous NSCLC.(4,5)

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "The DESTINY-Lung01 trial confirmed the HER2 mutation as an actionable
biomarker in non-small cell lung cancer. If approved, Enhertu has the
potential to become a new standard treatment in this patient population,
offering a much-needed option for patients with HER2-mutant metastatic
non-small cell lung cancer who currently have no targeted treatment options."

 

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The results of
DESTINY-Lung01 showed that Enhertu is the first HER2-directed therapy to
demonstrate a strong and robust tumour response in more than half of patients
with previously treated HER2-mutant metastatic non-small cell lung cancer.
Seeking approval in the US for a third tumour type in three years further
demonstrates the significant potential of Enhertu in treating multiple
HER2-targetable cancers."

 

The sBLA is based on data from the registrational DESTINY-Lung01 Phase II
trial published in The New England Journal of Medicine
(https://www.nejm.org/doi/full/10.1056/NEJMoa2112431) , and is supported by
the Phase I trial (DS8201-A-J101) published in Cancer Discovery
(https://aacrjournals.org/cancerdiscovery/article/10/5/688/2521/Targeting-HER2-with-Trastuzumab-Deruxtecan-A-Dose?searchresult=1)
.

 

Primary results from previously-treated patients with HER2-mutations (cohort
2) of DESTINY-Lung01 demonstrated a confirmed objective response rate (ORR) of
54.9% (95% confidence interval  CI : 44.2-65.4) in patients treated
with Enhertu (6.4mg/kg) as assessed by independent central review (ICR). One
(1.1%) complete response (CR) and 49 (53.8%) partial responses (PR) were
observed.

 

A confirmed disease control rate (DCR) of 92.3% was seen with a reduction in
tumour size observed in most patients. After a median follow-up of 13.1
months, the median duration of response (DoR) for Enhertu was 9.3 months. The
median progression-free survival (PFS) was 8.2 months and the median overall
survival (OS) was 17.8 months.

 

The safety profile of the most common adverse events with Enhertu in
DESTINY-Lung01 was consistent with previous clinical trials with no new safety
concerns identified.

 

Enhertu is being further assessed in a comprehensive clinical development
programme evaluating efficacy and safety across multiple HER2-targetable
cancers, including breast, gastric, lung and colorectal cancers.

 

Notes

 

HER2-mutant NSCLC

Lung cancer is the second most common form of cancer globally, with more than
two million new cases diagnosed in 2020.(2) In the US, lung cancer is the
second most commonly diagnosed cancer, with more than 236,000 new cases
expected in 2022.(6) For patients with metastatic NSCLC, prognosis is
particularly poor, as only approximately 8% 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 gene alterations (called HER2 mutations) have
been identified in NSCLC as distinct molecular targets and have been reported
in approximately 2-4% of patients with non-squamous NSCLC.(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.(7) HER2 gene mutations have been independently associated with cancer
cell growth and poor prognosis, with an increased incidence of brain
metastases.(8) Although the role of anti-HER2 treatment is well established in
breast and gastric cancers, HER2 is an emerging biomarker in NSCLC with no
approved HER2-directed therapies.(4,9) Next generation sequencing has been
utilised in the identification of HER2 (ERBB2) mutations.(10)

 

DESTINY-Lung01

DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial evaluating
the safety and efficacy of Enhertu in patients with HER2-mutant (6.4mg/kg) or
HER2-overexpressing (defined as IHC3+ or IHC2+) [6.4mg/kg and 5.4mg/kg]
unresectable and/or metastatic non-squamous NSCLC who had progressed after one
or more systemic therapies. The primary endpoint is confirmed ORR by ICR. Key
secondary endpoints include DoR, DCR, PFS, OS and safety. DESTINY-Lung01
enrolled approximately 180 patients at multiple sites, including Asia, Europe
and North America. For more information about the trial, visit
ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03505710) .

 

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 40 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 (6.4mg/kg) is approved in several 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
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 are currently under review in Europe,
Japan, the US and several other countries for the treatment of adult patients
with unresectable or metastatic HER2-positive breast cancer who have received
a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03
trial.

 

Enhertu also is currently under review in Europe for the treatment of adult
patients with locally advanced or metastatic HER2-positive gastric or GEJ
adenocarcinoma who have received a prior anti-HER2-based regimen based on the
DESTINY-Gastric01 and DESTINY-Gastric02 trials.

 

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 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 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 Twitter @AstraZeneca (https://twitter.com/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. FDA. Priority Review. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
Accessed April 2022.

2. WHO. International Agency of Cancer Research. Cancer Today. 2020. Available
at: https://gco.iarc.fr/today/home. Accessed April 2022.

3. American Cancer Society. Lung cancer survival rates. Available at:
https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html
. Accessed April 2022.

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. Campbell, JD, et al. Distinct patterns of somatic genome alterations in
lung adenocarcinomas and squamous cell carcinomas. Nature Genetics.
2016;48(6):607-16.

6. American Cancer Society. Key Statistics for Lung Cancer. Available at:
https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed
April 2022.

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

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

9. Zhou J, et al. Clinical outcomes of patients with HER2-mutant advanced lung
cancer: chemotherapies versus HER2-directed therapies. Ther Adv Med Oncol.
2020;12:1-9.

10. 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 Cyto 2019; 127 (7): 428-431.

 

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 (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCBKFBQDBKBPQD