REG - AstraZeneca PLC - Enhertu granted BTD for post-neoadjuvant early BC

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RNS Number : 3758M  AstraZeneca PLC  22 December 2025

22 December 2025

 

Enhertu granted Breakthrough Therapy Designation in the US as post-neoadjuvant
therapy for patients with HER2-positive early breast cancer

 

Tenth Breakthrough Therapy Designation for AstraZeneca and Daiichi Sankyo's
Enhertu with the latest based on DESTINY-Breast05 Phase III trial results

 

AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been
granted Breakthrough Therapy Designation (BTD) in the US for adult patients
with HER2-positive early breast cancer with residual invasive disease in the
breast and/or axillary lymph nodes after neoadjuvant treatment and high risk
of disease recurrence.

 

The Food and Drug Administration (FDA) BTD accelerates the development and
regulatory review of potential new medicines intended to treat a serious
condition and address a significant unmet medical need.

 

The FDA granted this BTD based on results from the DESTINY-Breast05
(https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-reduced-the-risk-of-disease-recurrence-or-death-by-53-vs-t-dm1-in-patients-with-high-risk-her2-positive-early-breast-cancer.html)
Phase III trial presented in a Presidential Symposium at the 2025 European
Society for Medical Oncology (ESMO) Congress and subsequently published in The
New England Journal of Medicine (https://www.nejm.org/) .

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D,
AstraZeneca, said: "For patients with residual disease after neoadjuvant
treatment, the post-neoadjuvant setting represents a critical opportunity to
reduce the risk of recurrence and prevent progression to metastatic disease.
This Breakthrough Therapy Designation highlights the impressive clinical
benefit of Enhertu over the current standard of care and underscores its
potential to become an important treatment option in the post-neoadjuvant
setting."

 

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "This tenth
Breakthrough Therapy Designation reinforces how Enhertu continues to deliver
transformational results that advance the treatment of breast cancer. We look
forward to working with the FDA with the goal of bringing Enhertu to the
post-neoadjuvant setting of HER2-positive early breast cancer, as
DESTINY-Breast05 clearly demonstrated that Enhertu may help halt invasive
disease recurrence over the current standard of care, resulting in potentially
more patients achieving a cure."

 

DESTINY-Breast05 is the second positive trial of Enhertu in early breast
cancer in 2025. The first trial, DESTINY-Breast11, evaluating patients with
high-risk HER2-positive disease in the neoadjuvant setting, is currently under
review by the FDA.

 

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

 

Notes

 

Post-neoadjuvant Treatment for HER2-Positive Early Breast Cancer

Breast cancer is the second most common cancer and one of the leading causes
of cancer-related deaths worldwide.1 More than two million breast cancer cases
were diagnosed in 2022, with more than 665,000 deaths globally.(1)

 

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the
surface of many types of tumours including breast cancer.(2) HER2 protein
overexpression may occur as a result of HER2 gene amplification and is often
associated with aggressive disease and poor prognosis in breast cancer.(2)
Approximately one in five cases of breast cancer are considered HER2
positive.(3)

 

For patients with HER2-positive early breast cancer, achieving pathologic
complete response (pCR) with neoadjuvant treatment is the earliest indicator
of improved long-term survival.(4) However, approximately half of patients who
receive neoadjuvant treatment do not experience pCR, putting them at increased
risk of disease recurrence.(5-9)

 

Despite receiving additional treatment with T-DM1 for residual disease in the
post-neoadjuvant setting, approximately 20% of patients still experience
invasive disease or death, with no reduction in the risk of central nervous
system recurrence.(10-11) Once patients are diagnosed with metastatic disease,
the five-year survival rate drops from nearly 90% to approximately 30%.1(2)

 

Post-neoadjuvant therapy represents a key opportunity to minimise the risk of
recurrence and prevent progression to metastatic disease for patients with
residual disease. New treatment options are needed in the early breast cancer
setting to help reduce the likelihood of disease progression and improve
long-term outcomes for more patients.(13,14)

 

DESTINY-Breast05

DESTINY-Breast05 is a global, multicentre, randomised, open-label, Phase III
trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus
trastuzumab emtansine (T-DM1) in patients with HER2-positive early breast
cancer with residual invasive disease in breast or axillary lymph nodes
following neoadjuvant therapy and a high risk of recurrence. High risk of
recurrence was defined as presentation with inoperable cancer (prior to
neoadjuvant therapy) or pathologically positive axillary lymph nodes following
neoadjuvant therapy.

 

The primary endpoint of DESTINY-Breast05 is investigator-assessed invasive
disease-free survival (IDFS). IDFS is defined as the time from randomisation
until first invasive local, axillary or distant recurrence or death from any
cause. The key secondary endpoint is investigator-assessed disease-free
survival. Other secondary endpoints include overall survival, distant
recurrence-free interval, brain metastases-free interval and safety.

 

DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North America,
Oceania and South America. For more information about the trial, visit
ClinicalTrials.gov
(https://clinicaltrials.gov/study/NCT04622319?term=Destiny-Breast05%20&rank=1)
.

 

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
number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via
tetrapeptide-based cleavable linkers.

 

Enhertu (5.4mg/kg) in combination with pertuzumab is approved in the US as a
1st-line treatment for adult patients with unresectable or metastatic
HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved
test based on the results from the DESTINY-Breast09
(https://clinicaltrials.gov/study/NCT04784715) trial.

 

Enhertu (5.4mg/kg) is approved in more than 90 countries/regions worldwide
for the treatment of adult patients with unresectable or metastatic
HER2-positive (IHC 3+ or ISH+) breast cancer who have received a 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 (https://clinicaltrials.gov/study/NCT03529110) trial.

 

Enhertu (5.4mg/kg) is approved in more than 85 countries/regions 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 (https://clinicaltrials.gov/study/NCT03734029) trial.

 

Enhertu (5.4mg/kg) is approved in more than 55 countries/regions worldwide
for the treatment of adult patients with unresectable or metastatic hormone
receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ ISH-) or HER2-ultralow
(IHC 0 with membrane staining) breast cancer, as determined by a locally or
regionally approved test, that have progressed on one or more endocrine
therapies in the metastatic setting based on the results from the
DESTINY-Breast06 (https://clinicaltrials.gov/study/NCT04494425) trial.

 

Enhertu (5.4mg/kg) is approved in more than 60 countries/regions worldwide for
the treatment of adult patients with unresectable or metastatic non-small cell
lung cancer (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
(https://www.clinicaltrials.gov/study/NCT04644237) and/or DESTINY-Lung05
(https://clinicaltrials.gov/study/NCT05246514) trials. Continued approval in
China and the US for this indication may be contingent upon verification and
description of clinical benefit in a confirmatory trial.

 

Enhertu (6.4mg/kg) is approved in more than 70 countries/regions worldwide
for the treatment of adult patients with locally advanced or metastatic
HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction
(GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based
on the results from the DESTINY-Gastric01
(https://clinicaltrials.gov/study/NCT03329690) , DESTINY-Gastric02
(https://clinicaltrials.gov/study/NCT04014075) and/or DESTINY-Gastric06
(https://clinicaltrials.gov/study/NCT04989816) trials. Continued approval in
China for this indication may be contingent upon verification and description
of clinical benefit in a confirmatory trial.

 

Enhertu (5.4mg/kg) is approved in more than 10 countries/regions worldwide for
the treatment of adult patients with unresectable or metastatic HER2-positive
(IHC 3+) solid tumours who have received prior systemic treatment and have no
satisfactory alternative treatment options based on efficacy results from the
DESTINY-PanTumor02 (https://clinicaltrials.gov/study/NCT04482309) ,
DESTINY-Lung01 (https://clinicaltrials.gov/study/NCT03505710) and
DESTINY-CRC02 (https://clinicaltrials.gov/study/NCT04744831) trials. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in a confirmatory trial.

 

Enhertu development programme
A comprehensive global clinical development programme is underway evaluating
the efficacy and safety of Enhertu as a monotherapy, in combination or
sequentially with other cancer medicines across multiple HER2-targetable
cancers.

 

Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly
develop and commercialise Enhertu 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 Datroway (datopotamab deruxtecan) 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 for each
ADC. Daiichi Sankyo is responsible for the manufacturing and supply
of Enhertu and Datroway.

 

AstraZeneca in breast cancer

Driven by a growing understanding of breast cancer biology, AstraZeneca is
challenging, and redefining, the current clinical paradigm for how breast
cancer is classified and treated to deliver even more effective treatments to
patients in need - with the bold ambition to one day eliminate breast cancer
as a cause of death.

 

AstraZeneca has a comprehensive portfolio of approved and promising compounds
in development that leverage different mechanisms of action to address the
biologically diverse breast cancer tumour environment.

 

With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes
in patients with HER2-positive, HER2-low and HER2-ultralow metastatic breast
cancer and are exploring its potential in earlier lines of treatment and in
new breast cancer settings.

 

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with
foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and
aims to reshape the HR-positive space with first-in-class AKT
inhibitor, Truqap (capivasertib), the TROP2-directed
ADC, Datroway (datopotamab deruxtecan), and next-generation oral SERD and
potential new medicine camizestrant.

 

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has
been studied in early and metastatic breast cancer patients with an
inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the
US and Canada) continue to research Lynparza in these settings. AstraZeneca
is also exploring the potential of saruparib, a potent and selective inhibitor
of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive,
HER2-negative advanced breast cancer.

 

To bring much-needed treatment options to patients with triple-negative breast
cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with
Daiichi Sankyo to evaluate the potential of Datroway alone and in combination
with immunotherapy Imfinzi (durvalumab).

 

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's innovative medicines are
sold in more than 125 countries and 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.   Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of
incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J
Clin. 2024; 74(3):229-263.

2.   Cheng X. A comprehensive review of HER2 in cancer biology and
therapeutics. Genes. 2024;15(7):903.

3.   Tarantino P, et al. ESMO expert consensus statements (ECS) on the
definition, diagnosis, and management of HER2-low breast cancer. J An Onc.
2023;34(8):645-659.

4.   Spring LM, et al. Pathological complete response after neoadjuvant
chemotherapy and impact on breast cancer recurrence and survival: a
comprehensive meta-analysis. Clin Cancer Res. 2020;26(12):2838-2284.

5.   Schneeweiss A, et al. Pertuzumab plus trastuzumab in combination with
standard neoadjuvant anthracycline-containing and anthracycline-free
chemotherapy regimens in patients with HER2-positive early breast cancer: a
randomized phase II cardiac safety study (TRYPHAENA). Annals of Oncol. 2013;
24:2278-2284.

6.   Swain S, et al. Pertuzumab, trastuzumab, and standard anthracycline-
and taxane-based chemotherapy for the neoadjuvant treatment of patients with
HER2-positive localized breast cancer (BERENICE): a phase II, open-label,
multicenter, multinational cardiac safety study. Annals of Oncology. 2018;
29:646-653.

7.   Huober J, et al. Atezolizumab With Neoadjuvant Anti-Human Epidermal
Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth
Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the
Randomized Phase III IMpassion050 Trial. J Clin Oncol. 2022; 40:2946-2956.

8.   Masuda N, et al. A randomized, 3-arm, neoadjuvant, phase 2 study
comparing docetaxel + carboplatin + trastuzumab + pertuzumab
(TCbHP), TCbHP followed by trastuzumab emtansine and pertuzumab (T-DM1+P), and
T-DM1+P in HER2-positive primary breast cancer. Breast Cancer Res Treat. 2020;
180:135-146.

9.   Gao H, et al. De-escalated neoadjuvant taxane plus trastuzumab and
pertuzumab with or without carboplatin in HER2-positive early breast cancer
(neoCARHP): A multicentre, open-label, randomised, phase 3 trial. Presented
ASCO Annual Meeting 2025.

10.  Geyer C, et al. Survival with Trastuzumab Emtansine in Residual
HER2-Positive Breast Cancer. N Engl J Med. 2025; 392:249-57.

11.  NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version
4.2025.

12.  National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer.
Available at: https://seer.cancer.gov/statfacts/html/breast.html
(https://seer.cancer.gov/statfacts/html/breast.html) . Accessed December 2025.

13.  Von Minckwitz G, et al. Trastuzumab emtansine for residual invasive
HER2-positive breast cancer. N Engl J Med. 2019; 380(7):617-628.

14.  Zaborowski AM, et al. Neoadjuvant systemic therapy for breast cancer. Br
J Surg. 2023; 110(7):765-772.

 

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

 

 

 

 

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