DATROWAY® Type II Variation Application Validated in the EU as First-Line Treatment for Patients with Metastatic Triple Negative Breast Cancer Who are Not Candidates for Immunotherapy

Key Terms

type II variation regulatory

A Type II variation is a regulatory classification for major changes to an approved drug, medical device, or its manufacturing that must be submitted to health authorities and approved before the change can be implemented. Like applying for a new building permit rather than filing a quick repair notice, this kind of change can delay product launches, raise costs, or alter supply; investors monitor these approvals because they can materially affect future revenue and business risk.

metastatic triple negative breast cancer medical

A form of breast cancer that has spread beyond the breast to other parts of the body and lacks three common molecular targets used by many treatments — estrogen receptor, progesterone receptor and HER2. Because it cannot be treated with several standard targeted drugs, it is harder to manage and often requires different, more intensive therapies; that makes progress in effective treatments especially important for investors tracking drug development, clinical trials, and potential market opportunities.

pd-1/pd-l1 inhibitor therapy medical

PD-1/PD-L1 inhibitor therapy is a type of cancer treatment that blocks a molecular “brake” cancer uses to hide from the immune system, allowing immune cells to recognize and attack tumors. For investors, these drugs matter because they can change clinical outcomes, drive large revenues or licensing deals, and create regulatory and trial milestones that materially affect a company’s valuation—think of them as turning on the body’s defense system to fight cancer.

trop2 medical

Trop2 is a protein found on the surface of many cancer cells that acts like a visible flag doctors and drugmakers can use to find and attack tumors. It matters to investors because drugs designed to bind Trop2 can deliver treatment directly to cancer cells, affecting how well a therapy works, which patients it helps, and the potential market and regulatory value of companies developing those targeted treatments.

antibody drug conjugate medical

An antibody drug conjugate is a targeted medical treatment that combines a special antibody with a powerful drug, allowing precise delivery of the medicine directly to cancer cells or other harmful cells in the body. For investors, it represents a sophisticated approach to therapy that could improve treatment effectiveness and reduce side effects, potentially leading to significant growth opportunities in the biotech and pharmaceutical sectors.

overall survival medical

Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.

progression-free survival medical

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

monotherapy medical

Monotherapy is a treatment approach that uses only one type of medicine or therapy to address a condition, instead of combining multiple options. For investors, understanding monotherapy matters because it can influence a company's development strategy, risk profile, and potential market size, especially if the single-treatment approach proves effective or faces limitations compared to combination therapies.

• Based on TROPION-Breast02 phase 3 trial results where Daiichi Sankyo and AstraZeneca’s DATROWAY is the first and only medicine to significantly improve overall survival versus chemotherapy in this patient population
• If approved, DATROWAY could become the standard of care in this setting

TOKYO & MUNICH--(BUSINESS WIRE)-- The European Medicines Agency (EMA) has validated the Type II Variation marketing authorization application for DATROWAY^® (datopotamab deruxtecan) as monotherapy for the first-line treatment of adult patients with unresectable or metastatic triple negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.

DATROWAY is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

The validation confirms the completion of the application and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use. The application is based on data from the TROPION-Breast02 phase 3 trial presented in a late-breaking proffered paper session at the 2025 European Society for Medical Oncology (#ESMO25) Congress. In the trial, DATROWAY demonstrated statistically significant and clinically meaningful improvement for the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to investigator’s choice of chemotherapy as first-line treatment for patients with metastatic TNBC for whom immunotherapy was not an option.

“DATROWAY has shown the potential to replace traditional chemotherapy and improve survival for patients with metastatic triple negative breast cancer, the most aggressive type of breast cancer with one of the worst prognoses,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “This EMA validation represents the potential for a second indication for DATROWAY in breast cancer and another step forward in the approval process in Europe.”

“Approximately seven of every ten patients with metastatic triple negative breast cancer are unable to receive immunotherapy due to the biology of their tumors or other factors. Chemotherapy remains the first-line standard of care for these patients,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “With this validation of our application for DATROWAY, based on the pivotal TROPION-Breast02 results, we have taken a meaningful step towards bringing these patients in Europe an alternative to traditional chemotherapy for the first time.”

Additional regulatory submissions for DATROWAY in this indication are underway globally.

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 PFS as assessed by blinded independent central review and OS. Secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response, 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 Triple Negative Breast Cancer
TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.^1,2 In Europe, TNBC represents 24% of all breast cancer cases, with an estimated 83,000 diagnoses each year.³ TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.^4,5,6 Metastatic TNBC is the most aggressive type of breast cancer and has one of the worst prognoses, with median OS of just 12 to 18 months and only about 14% of patients living five years following diagnosis.^4,7,8

While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.⁴ Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.⁴ For patients with metastatic disease with PD-L1 expressing tumors, the addition of immunotherapy to chemotherapy has improved outcomes in the first-line setting.^9,10 However, for approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, chemotherapy remains the first-line standard of care.^11,12

TROP2 is a protein broadly expressed in several solid tumors, including TNBC.¹³ TROP2 is associated with increased tumor progression and poor survival in patients with breast cancer.^{14, 15}

About DATROWAY
DATROWAY (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific 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 35 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 Russia 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 DATROWAY Clinical Development Program
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 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 eight ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo.

The DXd ADC Technology platform of Daiichi Sankyo consists of six 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 is being developed by Daiichi Sankyo.

Additional ADCs being developed by Daiichi Sankyo include DS-9606, which consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload and DS3610, which consists of an antibody attached to a novel immunomodulatory payload that acts as an agonist of STING.

Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS-9606 and DS3610 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 is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit www.daiichisankyo.com.

References

¹ O’Reilly D, et al. World J Clin Oncol. 2021;12(3):164-182.
² World Health Organization. Breast Cancer. Accessed December 2025.
³ GLOBOCAN 2022. Global Cancer Observatory: World. Accessed December 2025.
⁴ American Cancer Society. Triple-Negative Breast Cancer. Accessed December 2025.
⁵ Martinez M, et al. Breast Cancer Res Treat. 2017;166(1):185-193.
⁶ Vargas L, et al. Cancer Epidemiol Biomarkers Prev. 2019;28(11):1771-1783.
⁷ National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes. Accessed December 2025.
⁸ Huppert L, et al. Ther Adv Med Oncol. 2022;14:1-25.
⁹ Cortes J, et al. N Engl J Med. 2022;387:217-226.
¹⁰ Geurts V, et al. Curr Treat Options Oncol.2023; 24:628-643.
¹¹ Punie K, et al. The Oncologist. 2025;30(3): oyaf034.
¹² National Comprehensive Cancer Network. Breast Cancer. V4.2025; April 17, 2025. Accessed December 2025.
¹³ Rossi V, et al. Front Immunol. 2024 Aug;15: 1447280.
¹⁴ Lin H, et al. Exp Mol Pathol. 2013:94(1): 73-78.
¹⁵ Goldenberg D, et al. Oncotarget. 2018;9(48): 28989-29006.

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