REG - AstraZeneca PLC - Enhertu improved IDFS in early BC in DB-05

AstraZenecaAnnouncement

29/09/2025 07:30

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RNS Number : 1069B  AstraZeneca PLC  29 September 2025

 

29 September 2025

 

Enhertu demonstrated highly statistically significant and clinically
meaningful improvement in invasive disease-free survival vs. T-DM1 in
DESTINY-Breast05 Phase III trial in patients with high-risk early breast
cancer following neoadjuvant therapy

 

Second positive Phase III trial of AstraZeneca and Daiichi Sankyo's Enhertu in
HER2-positive early breast cancer reinforces its potential to become a
foundational treatment option in curative-intent setting

 

Results from the DESTINY-Breast05 and DESTINY-Breast11 trials

will be presented at ESMO 2025 in a Presidential Symposium

 

Positive high-level results from a planned interim analysis of the
DESTINY-Breast05 Phase III trial showed Enhertu (trastuzumab deruxtecan)
demonstrated a highly statistically significant and clinically meaningful
improvement in invasive disease-free survival (IDFS) versus trastuzumab
emtansine (T-DM1) in patients with HER2-positive early breast cancer with
residual invasive disease in the breast or axillary lymph nodes after
neoadjuvant treatment and a high risk of disease recurrence. This is the
second positive Phase III trial of Enhertu in the HER2-positive early breast
cancer setting following positive results from the DESTINY-Breast11
(https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-improved-pcr-in-early-stage-breast-cancer.html)
Phase III neoadjuvant trial earlier this year.

 

Overall survival (OS) was not mature at the time of this planned interim
analysis and will be assessed at a subsequent analysis.

 

Currently, approximately half of patients with HER2-positive early breast
cancer have residual disease following neoadjuvant treatment, putting them at
an increased risk of disease recurrence.(1-7) Despite receiving additional
treatment in the post-neoadjuvant setting with current standards of care, some
patients still ultimately experience tumour progression to metastatic
disease.(8-10) 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.(10-11)

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D,
AstraZeneca, said: "This landmark trial is the first to directly compare
Enhertu and T-DM1 in early breast cancer, and the results clearly show that
Enhertu delivers superior outcomes, indicating that it may be a better option
for patients with high-risk HER2-positive disease in the post-neoadjuvant
setting. These results from DESTINY-Breast05, coupled with DESTINY-Breast11,
underscore our commitment to moving Enhertu into early-stage HER2-positive
breast cancer where patients can achieve sustained long-term outcomes,
increasing the opportunity for cure."

 

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "In patients with
early breast cancer with residual disease following neoadjuvant treatment, it
is critical to optimise treatment as this represents the last opportunity to
prevent progression to metastatic disease. The results of DESTINY-Breast05
demonstrate that treatment with Enhertu following surgery increases the length
of time patients are able to live free of invasive disease compared to the
existing standard of care, potentially offering patients with HER2-positive
early breast cancer a new treatment approach in this curative-intent setting."

 

The safety profile of Enhertu observed in DESTINY-Breast05 was consistent with
its known profile with no new safety concerns identified.

 

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.

 

Data from DESTINY-Breast05 (Abstract #LBA1) and DESTINY-Breast11 (Abstract
#291O) will be presented during Presidential Symposium 1
(https://cslide.ctimeetingtech.com/esmo2025/attendee/confcal/show/session/114)
on 18 October at the upcoming European Society for Medical Oncology (ESMO)
Congress 2025. The DESTINY-Breast05 data will also be shared with global
regulatory authorities.

 

DESTINY-Breast05 was conducted in collaboration with the National Surgical
Adjuvant Breast and Bowel Project Foundation (NSABP), the German Breast Group
(GBG), Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B) and SOLTI Breast
Cancer Research Group.

 

Notes

 

HER2-positive early breast cancer

Breast cancer is the second most common cancer and one of the leading causes
of cancer-related deaths worldwide.(12) More than two million breast cancer
cases were diagnosed in 2022, with more than 665,000 deaths globally.(12)

 

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the
surface of many types of tumours including breast cancer.(13) 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.(14)
Approximately one in five cases of breast cancer are considered
HER2-positive.(15)

 

Currently, approximately half of patients with HER2-positive early breast
cancer have residual disease following neoadjuvant treatment, putting them at
an increased risk of disease recurrence.(1-7) Despite receiving additional
treatment in the post-neoadjuvant setting, some patients still ultimately
experience tumour progression to metastatic disease.(8-10) Once patients are
diagnosed with metastatic disease, the five-year survival rate drops from
nearly 90 percent to approximately 30 percent.(16) New treatment options are
needed in the early breast cancer setting to help reduce the likelihood of
disease progression in order to improve long-term outcomes for more
patients.(10-11)

 

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 ematansine (T-DM1) in patients with HER2-positive primary breast
cancer that are at high risk of recurrence and have residual invasive disease
in breast or axillary lymph nodes following neoadjuvant therapy. 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 IDFS. IDFS
is defined as the time from randomisation until first occurrence of invasive
breast cancer recurrence, distant recurrence, or death from any cause.  The
key secondary endpoint is investigator-assessed disease-free survival. Other
secondary endpoints include OS, distant recurrence-free interval, brain
metastases-free interval and safety.

 

DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, Oceania, North
America 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) is approved in more than 85 countries/regions worldwide
for the treatment of adult patients with unresectable or metastatic
HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation  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/ct2/show/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/ct2/show/NCT03734029)
trial.

 

Enhertu (5.4mg/kg) is approved in more than 45 countries/regions 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?term=DESTINY-Lung02&rank=1)
 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 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/ct2/show/NCT03329690) , DESTINY-Gastric02
(https://clinicaltrials.gov/ct2/show/NCT04014075)  and/or DESTINY-Gastric06
(https://clinicaltrials.gov/study/NCT04989816)  trials. Continued approval in
China for this indication may by contingent upon verification and description
of clinical benefit in a confirmatory trial.

 

Enhertu (5.4mg/kg) is approved in more than 10 countries/regions 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://classic.clinicaltrials.gov/ct2/show/NCT04482309) , DESTINY-Lung01
(https://clinicaltrials.gov/study/NCT03505710)  and DESTINY-CRC02
(https://www.clinicaltrials.gov/study/NCT04744831?term=DESTINY-CRC02&rank=1)
 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 monotherapy across multiple
HER2-targetable cancers. Trials in combination with other anti-cancer
treatments, such as immunotherapy, also are underway.

 

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 previously treated 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
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.

 
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References

1.   Gianni L, et al. Efficacy and safety of neoadjuvant pertuzumab and
trastuzumab in women with locally advanced, inflammatory, or early
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2.   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.

3.   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.

4.   Hurvitz S, et al. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in
Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year
Outcomes From the Phase III KRISTINE Study. J Clin Oncol. 2019; 37:2206-2216.

5.   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.

6.   Masuda N, et al. A randomized, 3-arm, neoadjuvant, phase 2 study
comparing docetaxel + carboplatin + trastuzumab + pertuzumab
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7.   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
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8.   Von Minckwitz G, et al. Trastuzumab Emtansine for Residual Invasive
HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617-628

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

10.  NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version
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11.  Zaborowski AM, et al. Neoadjuvant systemic therapy for breast cancer. Br
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12.  Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of
incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer
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13.  Cheng X. A comprehensive review of HER2 in cancer biology and
therapeutics. Genes. 2024;15(7):903.

14.  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.

15.  Ahn S, et al. HER2 status in breast cancer: changes in guidelines and
complicating factors for interpretation. J Pathol Transl Med.
2019;54(1):34-44.

16.  National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer
Subtypes. Available at:
https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed
September 2025

 

Matthew Bowden
Company Secretary
AstraZeneca PLC

 

 

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