第一三共 Enhertu 与 Datroway 在日本获批两项转移性乳腺癌一线新适应症

Enhertu® and Datroway® Approved in Japan for Two New First-Line
Indications for Patients with Metastatic Breast Cancer

• Enhertu approval based on DESTINY-Breast09 phase 3 trial where Enhertu in combination with pertuzumab
reduced the risk of disease progression or death by 44% versus THP with a median progression-free survival
exceeding three years in first-line HER2 positive metastatic breast cancer
• Datroway approval based on TROPION-Breast02 phase 3 trial where Datroway demonstrated a median
overall survival of approximately two years versus chemotherapy in patients with first-line triple negative breast
cancer who are not candidates for PD-1/PD-L1 inhibitor therapy
• These approvals underscore the strength of the DXd ADC portfolio of Daiichi Sankyo to change the standard
of care across different subtypes of metastatic breast cancer in Japan

Tokyo – (September 16, 2026) – Enhertu® (trastuzumab deruxtecan) and Datroway® (datopotamab deruxtecan)
have been approved in Japan for two new indications in the first-line setting of patients with metastatic breast
cancer.

Enhertu in combination with pertuzumab was approved for the treatment of adult patients with HER2 positive
unresectable or recurrent breast cancer. Datroway was approved for the treatment of adult patients with hormone
receptor (HR) negative and HER2 negative unresectable or recurrent breast cancer, a subtype commonly referred
to as triple negative breast cancer (TNBC).

Enhertu and Datroway are specifically engineered DXd antibody drug conjugates (ADC) discovered by Daiichi
Sankyo (TSE: 4568) and being developed and commercialized by Daiichi Sankyo in Japan.

Breast cancer is the most common cancer among women in Japan.1 Both HER2 positive and TNBC are
aggressive breast cancer subtypes, with only about 30% and 15% of patients, respectively, living five years
following diagnosis.2,3 For patients with these aggressive subtypes, treatments that significantly delay disease
progression in the first-line metastatic setting are needed to improve long-term outcomes.

“These two approvals represent significant advances for the treatment of metastatic breast cancer. Enhertu in
combination with pertuzumab is the first new treatment regimen in more than a decade for patients with metastatic
HER2 positive disease and Datroway is the only TROP2 directed medicine to demonstrate an overall survival
benefit for patients with metastatic triple negative breast cancer in the first-line setting,” said Yuki Abe, PhD, Senior
Executive Officer, Head of R&D Division in Japan and Head of Research, Daiichi Sankyo. “With these new
approvals of Enhertu and Datroway, there are now two Daiichi Sankyo medicines available in Japan that can be
used as first-line treatments across the most aggressive subtypes of metastatic breast cancer.”

Data Supporting Enhertu Approval
The approval of Enhertu by Japan’s Ministry of Health, Labour and Welfare (MHLW) is based on results from the
DESTINY-Breast09 phase 3 trial. In the trial, Enhertu in combination with pertuzumab reduced the risk of disease
progression or death by 44% versus taxane, trastuzumab and pertuzumab (THP) (hazard ratio [HR]=0.56; 95%
confidence interval [CI]: 0.44-0.71; p<0.00001) in patients (n=383) with HER2 positive metastatic breast cancer
who had not received prior chemotherapy or HER2 targeted therapy or had received neoadjuvant or adjuvant
HER2 targeted therapy more than six months before the diagnosis of advanced or metastatic disease. Median
progression-free survival (PFS) was 40.7 months (95% CI: 36.5-not estimable [NE]) with Enhertu in combination
with pertuzumab compared to 26.9 months (95% CI: 21.8-NE) with THP as assessed by blinded independent
central review (BICR). These data were presented at the 2025 American Society of Clinical Oncology Annual
Meeting and subsequently published in The New England Journal of Medicine.

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In DESTINY-Breast09, the safety profile of Enhertu was consistent with previous clinical trials with no new safety
concerns identified. Adverse reactions occurred in 373 patients (97.9%) treated with Enhertu (5.4 mg/kg) in
combination with pertuzumab including 39 Japanese patients. The most common adverse reactions were nausea
(71.1%), diarrhea (55.9%), alopecia (46.2%), vomiting (42.0%) and anemia (34.9%). Interstitial lung disease (ILD)
occurred in 33.3% of Japanese patients treated with Enhertu in combination with pertuzumab as determined by an
independent ILD adjudication committee.

Data Supporting Datroway Approval
The approval of Datroway by Japan’s MHLW is based on results from the TROPION-Breast02 phase 3 trial, which
included patients with metastatic TNBC who experienced early relapse following prior treatment and were not
candidates for PD-1/PD-L1 inhibitor therapy. In this trial, Datroway demonstrated a statistically significant and
clinically meaningful 5.0 month improvement in median overall survival (OS) versus investigator’s choice of
chemotherapy (HR=0.79; 95% CI: 0.64-0.98; p=0.029). Median OS was 23.7 months for patients treated with
Datroway versus 18.7 months for those treated with chemotherapy. Datroway reduced the risk of disease
progression or death by 43% compared to chemotherapy (HR=0.57; 95% CI: 0.47-0.69; p<0.0001) as assessed by
BICR. Median PFS was 10.8 months for patients treated with Datroway versus 5.6 months for those treated with
chemotherapy. These data were presented at the 2025 European Society for Medical Oncology Congress and
subsequently published in Annals of Oncology.

In TROPION-Breast02, the safety profile of Datroway was consistent with previous clinical trials with no new safety
concerns identified. Adverse reactions occurred in 296 patients (92.8%) treated with Datroway (6 mg/kg) including
17 Japanese patients. The most common adverse reactions included stomatitis (57.1%), nausea (44.5%), alopecia
(40.8%), dry eye (23.8%) and constipation (22.6%). ILD was not observed in the 17 Japanese patients treated with
Datroway.

Both Enhertu and Datroway are approved in Japan with a Warning in their prescribing information for ILD. ILD
occurred in 11.7% of patients treated with Enhertu and 3.1% of patients treated with Datroway across multiple
clinical trials. As cases of ILD, including fatal cases, have occurred in Enhertu and Datroway treated patients, both
medicines are to be used in close collaboration with a respiratory disease expert. Patients should be closely
observed during therapy by monitoring for early signs or symptoms of ILD (such as dyspnea, cough or fever) and
performing periodical percutaneous oxygen saturation (SpO2) tests, chest X-ray scans and chest CT scans. If
abnormalities are observed, discontinue administration of Enhertu or Datroway and take appropriate measures,
such as corticosteroid administration. Prior to initiation of Enhertu or Datroway therapy, a chest CT scan should be
performed and medical history taken to confirm the absence of any comorbidity or history of ILD with the patient
and carefully consider the eligibility of the patient for Enhertu or Datroway therapy.

About DESTINY-Breast09
DESTINY-Breast09 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and
safety of Enhertu (5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP as first-
line treatment in patients with HER2 positive metastatic breast cancer.

Patients were randomized 1:1:1 to receive either Enhertu monotherapy with a pertuzumab matching placebo;
Enhertu in combination with pertuzumab; or THP. Randomization was stratified by prior treatment (de novo
metastatic disease versus progression from early-stage disease), HR status and PIK3CA mutation status.

The primary endpoint of DESTINY-Breast09 is PFS as assessed by BICR in the Enhertu monotherapy and
Enhertu combination arms. Secondary endpoints include investigator-assessed PFS, OS, overall response rate
(ORR), duration of response (DoR), pharmacokinetics and safety. The investigational arm assessing Enhertu
monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.

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DESTINY-Breast09 enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, North America and South
America. For more information about the trial, visit ClinicalTrials.gov.

About TROPION-Breast02
TROPION-Breast02 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and
safety of Datroway versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine,
carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for
whom immunotherapy was not an option. This included patients whose tumors did not express PD-L1 as well as
patients with PD-L1 expressing tumors who could not receive immunotherapy due to prior exposure in early-stage
disease, comorbidities or immunotherapy not being accessible in their geography. Enrollment included patients
with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such
as stable brain metastases.

The dual primary endpoints of TROPION-Breast02 are OS and PFS as assessed by BICR. Secondary endpoints
include PFS as assessed by investigator, ORR, DoR, disease control rate, pharmacokinetics and safety.

TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America. For
more information visit ClinicalTrials.gov.

About Metastatic Breast Cancer
Breast cancer is the most common cancer in women and the leading cause of cancer-related deaths among
women worldwide.4 Approximately 2.4 million breast cancer cases were diagnosed in 2024, with more than
690,000 deaths globally.4 In Japan, breast cancer is the most common cancer in women, with approximately
94,000 cases diagnosed and 16,800 deaths in 2024.1

There are three main breast cancer subtypes: HR positive, HER2 positive and TNBC.2,5,6 Approximately 15% to
20% of breast cancer cases are considered HER2 positive where the disease is driven by overexpression or
amplification of HER2, and 15% are considered to be triple negative where the tumor tests negative for estrogen
receptors, progesterone receptors or overexpression of HER2.7,8 Both HER2 positive and TNBC are aggressive
breast cancer subtypes, with only about 30% and 15% of patients, respectively, living five years following
diagnosis.2,3

While HER2 targeted therapies have improved outcomes for patients with HER2 positive metastatic breast cancer,
prognosis remains poor with most patients experiencing disease progression within two years of first-line treatment
with THP, which has been the standard of care for more than a decade.9,10,11,12

For patients with metastatic TNBC with PD-L1 expressing tumors, the addition of immunotherapy to chemotherapy
has improved outcomes in the first-line setting.13,14 However, for approximately 70% of patients with metastatic
TNBC who are not candidates for immunotherapy, chemotherapy was the standard first-line treatment.15

About Enhertu
Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC.
Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Enhertu is the lead ADC in the oncology
portfolio of Daiichi Sankyo and the most advanced program 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 (5.4 mg/kg) followed by THP is approved in Brazil, China, India, Singapore, Taiwan and the U.S. as a
neoadjuvant treatment for adult patients with HER2 positive (IHC 3+ or ISH+) stage 2 or stage 3 breast cancer

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based on the results from the DESTINY-Breast11 trial. Continued approval in China for this indication may be
contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (5.4 mg/kg) is approved in Brazil, Canada, India and the U.S. for the adjuvant treatment of adult patients
with HER2 positive breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or
without pertuzumab) and taxane-based treatment based on the DESTINY-Breast05 trial.

Enhertu (5.4 mg/kg) in combination with pertuzumab is approved in more than 40 countries/regions worldwide as a
first-line treatment for adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer,
as determined by a locally or regionally approved test, based on the results from the DESTINY-Breast09 trial.

Enhertu (5.4 mg/kg) is approved in more than 100 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 trial.

Enhertu (5.4 mg/kg) is approved in more than 75 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic hormone receptor 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 trial.

Enhertu (5.4 mg/kg) is approved in more than 100 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 trial.

Enhertu (5.4 mg/kg) is approved in more than 80 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors 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 and/or DESTINY-Lung05 trials. Continued approval in China and
the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory
trial.

Enhertu (6.4 mg/kg) is approved in more than 90 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, DESTINY-Gastric02 and/or DESTINY-Gastric04 trials.

Enhertu (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment
and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02,
DESTINY-Lung01, DESTINY-CRC02 and/or HERALD trials. Continued approval in the U.S. for this indication may
be contingent upon verification and description of clinical benefit in a confirmatory trial.

About Datroway
Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC.
Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Datroway is one of seven DXd ADCs in
the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific

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platform. Datroway is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in
collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an
exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Datroway (6 mg/kg) is approved in more than 30 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy based on the
results from the TROPION-Breast02 trial.

Datroway (6 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who
have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on
the results from the TROPION-Breast01 trial.

Datroway (6 mg/kg) is approved in Brazil, Russia, Singapore and the U.S. for the treatment of adult patients with
locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior
EGFR-directed therapy and platinum-based chemotherapy, based on the results from TROPION-Lung05 and
TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and
description of clinical benefit in a confirmatory trial.

About the Enhertu and Datroway Clinical Development Programs
A comprehensive global clinical development program is underway with more than 30 trials evaluating the efficacy
and safety of Enhertu across multiple cancers, including breast, NSCLC, gastric, colorectal, biliary tract, ovarian,
endometrial cancers. The program includes nine phase 3 trials in breast cancer, two phase 3 trials in NSCLC, two
phase 3 trials in gastric cancer, two phase 3 trials in endometrial cancer, one phase 3 trial in ovarian cancer and
one phase 3 trial in BTC evaluating Enhertu as a monotherapy and in combination or sequentially with other
cancer treatments in various settings.

A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy
and safety of Datroway across multiple cancers, including NSCLC, TNBC and urothelial cancer. The program
includes eight phase 3 trials in lung cancer, five phase 3 trials in breast cancer, and one phase 3 trial and one
phase 2/3 trial in urothelial cancer evaluating Datroway as a monotherapy and in combination with other cancer
treatments in various settings.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize Enhertu
in March 2019 and Datroway in July 2020, 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.

About the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of nine ADCs in clinical development crafted from ADC technology
discovered in-house by Daiichi Sankyo.

The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each
ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an
exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include Enhertu and Datroway,
which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan
(I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly
developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939 and DS3790 are being
developed by Daiichi Sankyo.

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Additional ADCs being developed by Daiichi Sankyo include DS3610, which consists of an antibody attached to a
novel payload that acts as an agonist of STING, and DS1025, which consists of a CD25 directed antibody
attached to an immuno-oncology optimized cytotoxic payload.

Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610, DS3790 and DS1025
are investigational medicines that have not been approved for any indication in any country. Safety and efficacy
have not been established.

About Daiichi Sankyo
Daiichi Sankyo (TSE: 4568) is a global healthcare company committed to becoming a trusted healthcare innovator,
transforming the lives of people through its strength in science and technology. The company discovers and
develops new standards of care to address diverse medical needs to fulfill its purpose of contributing to the
enrichment of quality of life around the world. With a strategic focus on oncology, Daiichi Sankyo is advancing an
industry-leading antibody drug conjugate portfolio along with identifying new breakthrough generating technologies
to deliver practice-changing medicines to patients, healthcare professionals and society. For more information,
please visit www.daiichisankyo.com.

MEDIA CONTACTS: INVESTOR RELATIONS CONTACT:
Global: [email protected]
Jennifer Brennan
[email protected]
+ 1 908 900 3183 (mobile)

Japan:
[email protected]

:

REFERENCES:
1 Globocan 2024. Japan Fact Sheet. Accessed September 2026.
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3 National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes. Accessed September 2026.
4 World Health Organization. Global Status Report On Cancer 2026: The Future We Choose Together. Accessed September 2026.
5 American Cancer Society. Breast Cancer Hormone Receptor Status. Accessed September 2026.
6 American Cancer Society. Breast Cancer HER2 Status. Accessed September 2026.
7 O’Reilly D, et al. World J Clin Oncol. 2021;12(3):164-182.

8 Tarantino P, et al. Ann Oncol. 2023;34(8):645-659.
9 Swain SM, et al. Lancet Oncol. 2020;21(4):519-530.
10 Blumenthal G, et al. Clinical Cancer Research. 2013;19(18).
11 Tripathy D, et al. Oncologist. 2020;25(2):e214-e222.
12 Aihara T, et al. Breast Cancer. 2015;22:1-4.

13 Cortes J, et al. N Engl J Med. 2022;387:217-226.
14 Geurts V, et al. Curr Treat Options Oncol. 2023;24:628-643.
15 Punie K, et al. Oncologist. 2025;30(3):oyaf034.

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