Datroway® Receives U.S. FDA Approval as First TROP2-Directed Antibody Drug Conjugate for First-Line Treatment of Metastatic Triple-Negative Breast Cancer in Patients Not Eligible for PD-1/PD-L1 Inhibitor Therapy
Daiichi Sankyo and AstraZeneca announced that Datroway (datopotamab deruxtecan-dlnk) has received approval in the United States for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy. This marks a significant advancement in the treatment landscape for a patient population that has historically faced limited first-line treatment options beyond chemotherapy.
Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC), discovered by Daiichi Sankyo and co-developed and commercialized in collaboration with AstraZeneca. It is designed to deliver a cytotoxic payload directly to cancer cells expressing the TROP2 protein, thereby maximizing tumor cell destruction while minimizing exposure to healthy tissues.
The U.S. Food and Drug Administration (FDA) granted approval following Priority Review, supported by data from the pivotal Phase 3 TROPION-Breast02 clinical trial. Results from this study were previously presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in the journal Annals of Oncology.
Clinical Significance of the Approval
Triple-negative breast cancer is one of the most aggressive subtypes of breast cancer and is characterized by the absence of estrogen receptors, progesterone receptors, and HER2 protein expression. This makes it unresponsive to many commonly used targeted therapies. Patients with metastatic TNBC often experience rapid disease progression and poor overall survival outcomes compared to other breast cancer subtypes.
For many patients who are not eligible for immunotherapy using PD-1 or PD-L1 inhibitors—due to tumor biology, prior treatment history, comorbid conditions, or lack of access—chemotherapy has remained the standard first-line treatment. The approval of Datroway introduces a new targeted treatment option that has demonstrated meaningful survival benefits over chemotherapy in this setting.
TROPION-Breast02 Trial Results
The approval is primarily based on the results of the TROPION-Breast02 Phase 3 clinical trial, a global, randomized, open-label study designed to evaluate the efficacy and safety of Datroway compared with investigator’s choice of chemotherapy.
The trial enrolled 644 patients across multiple regions including Africa, Asia, Europe, North America, and South America. Participants included individuals with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included both PD-L1–negative patients and those who, despite PD-L1 expression, were ineligible for immunotherapy due to prior exposure in early-stage disease, underlying medical conditions, or geographic limitations in access.
The dual primary endpoints of the study were progression-free survival (PFS), assessed by blinded independent central review (BICR), and overall survival (OS). Secondary endpoints included investigator-assessed PFS, objective response rate (ORR), duration of response, disease control rate, pharmacokinetics, and safety.
Survival Benefit and Efficacy Outcomes
Results from the study demonstrated that Datroway significantly improved survival outcomes compared with standard chemotherapy.
Patients treated with Datroway achieved a median overall survival of 23.7 months compared with 18.7 months in those treated with chemotherapy. This represented a 5.0-month improvement in median overall survival, with a hazard ratio (HR) of 0.79 (95% confidence interval [CI]: 0.64–0.98; p=0.0290). This finding is particularly notable in metastatic TNBC, where treatment options have historically provided limited survival extension.
In addition to overall survival benefits, Datroway demonstrated a substantial improvement in progression-free survival. Median PFS was 10.8 months in the Datroway arm compared to 5.6 months in the chemotherapy arm, representing a 43% reduction in the risk of disease progression or death (HR=0.57; 95% CI: 0.47–0.69; p<0.0001).
The objective response rate was also significantly higher in patients receiving Datroway. The ORR was 64% in the Datroway group compared to 30% in the chemotherapy group, indicating a markedly improved tumor response profile. These results further support the clinical activity of Datroway in this difficult-to-treat patient population.
Expert Commentary and Clinical Impact
Clinical experts involved in the trial have emphasized the importance of these results. According to investigators, Datroway represents the first therapy in this setting to demonstrate a statistically significant improvement in overall survival compared with chemotherapy in first-line metastatic TNBC patients who are not eligible for immunotherapy.
The observed median overall survival of nearly two years is particularly significant in metastatic TNBC, where survival outcomes have historically been far lower. Experts suggest that this improvement may signal a potential shift in treatment expectations for this disease.
Patient advocacy groups have also highlighted the importance of expanding treatment options beyond chemotherapy. For many individuals with metastatic TNBC, especially those who cannot receive immunotherapy, treatment decisions have been limited, leaving a critical unmet need in this population.
Safety Profile
The safety of Datroway was evaluated in 319 patients with TNBC who received the 6 mg/kg dose in the TROPION-Breast02 study. The treatment’s safety profile was consistent with known effects of antibody-drug conjugates, particularly those targeting rapidly dividing cancer cells.
The most commonly reported adverse reactions (occurring in 20% or more of patients) included stomatitis, nausea, alopecia, fatigue, constipation, musculoskeletal pain, dry eye, vomiting, and hematologic abnormalities such as decreased hemoglobin, white blood cells, lymphocytes, neutrophils, and sodium levels. Increased liver enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase were also observed.
Serious adverse reactions occurred in 17% of patients receiving Datroway. The most common serious events included pneumonia, vomiting, COVID-19 infection, and anemia. One fatal case of interstitial lung disease/pneumonitis was reported in the study population, highlighting the need for careful monitoring of pulmonary symptoms during treatment.
Mechanism and Development
Datroway is a TROP2-directed antibody drug conjugate built on Daiichi Sankyo’s proprietary DXd ADC technology platform. It works by binding to TROP2, a protein commonly expressed on the surface of various cancer cells, including triple-negative breast cancer cells. Once bound, the drug is internalized, releasing a potent cytotoxic agent that induces DNA damage and leads to cancer cell death.
The ADC is jointly developed by Daiichi Sankyo and AstraZeneca, combining Daiichi Sankyo’s expertise in ADC design with AstraZeneca’s global oncology development and commercialization capabilities.
Regulatory Pathway and Global Review
The FDA approval was granted under Priority Review and is part of Project Orbis, an international collaborative review framework for oncology therapies. Through this initiative, regulatory agencies in Australia, Canada, Singapore, and Switzerland are also reviewing the therapy. Additional regulatory submissions are ongoing in the European Union, China, and Japan.
This coordinated approach is designed to accelerate global access to promising cancer therapies and ensure timely availability for patients worldwide.
Guidelines Inclusion and Access
Following the strong results of TROPION-Breast02, Datroway has been incorporated into the NCCN Clinical Practice Guidelines in Oncology as a Category 1 Preferred first-line treatment option for patients with metastatic TNBC who are not eligible for immunotherapy.
To support patient access, Daiichi Sankyo and AstraZeneca have also introduced assistance programs in the United States, including reimbursement support, patient navigation services, and distribution assistance. More information is available through dedicated support channels established for healthcare providers and patients.
The approval of Datroway represents a major milestone in the treatment of metastatic triple-negative breast cancer. By demonstrating a meaningful improvement in overall survival, progression-free survival, and response rates compared with chemotherapy, the therapy introduces a new standard of care for patients who previously had limited first-line treatment options.
With its novel TROP2-targeted mechanism and clinically validated efficacy, Datroway is positioned to reshape the treatment paradigm in metastatic TNBC and potentially expand into broader oncology applications as further research continues.
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.
