Dato-DXd Granted Priority Review as First-Line Therapy for Metastatic Triple-Negative Breast Cancer

The FDA granted priority review to a supplemental Biologic License Application (sBLA) for datopotamab deruxtecan-dlnk (Dato-DXd, Datroway; AstraZeneca, Daiichi Sankyo) as a first-line treatment for patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.¹ Priority review designation is reserved for therapies that may offer significant improvements in safety or effectiveness over existing treatment options, emphasizing the potential clinical impact of Dato-DXd in this patient population.¹

The sBLA is supported by data from the phase 3 TROPION-Breast02 trial (NCT05374512), which compared Dato-DXd to investigator's choice chemotherapy in patients with locally recurrent inoperable or metastatic TNBC who were previously untreated and immunotherapy-ineligible. In the trial, Dato-DXd led to an improvement in overall survival that was both statistically significant and clinically meaningful in comparison to chemotherapy, with a median overall survival difference of approximately 5 months.² Additionally, Dato-DXd markedly lowered the risk of disease progression or death, demonstrating its potential to bring about better long-term outcomes for patients with historically limited therapeutic success.¹

The Role of Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic strategy in oncology, offering targeted delivery of cytotoxic agents to cancer cells while limiting systemic exposure. Dato-DXd is a trophoblast cell surface antigen 2 (TROP2)-directed ADC designed to address the unmet need in patients with metastatic TNBC. TROP2 is a transmembrane glycoprotein that is highly expressed across TNBC tumors, making it an attractive therapeutic target. Dato-DXd combines a humanized monoclonal antibody targeting TROP2 with a potent topoisomerase I inhibitor payload, delivered via a cleavable linker that enables selective intracellular release of the cytotoxic agent following tumor cell internalization.²

Efficacy Outcomes and Clinical Implications

Besides just an improvement in overall survival, Dato-DXd also demonstrated better progression-free survival and higher objective response rates versus chemotherapy in the trial.¹ These outcomes are notable considering the historically limited benefits of chemotherapy in metastatic TNBC. Dato-DXd’s long-lasting responses add to the justification of the clinical targeted ADC therapy relevance in this setting.

Patients with metastatic TNBC who do not qualify for immunotherapy represent a significant portion of the overall TNBC population. For these patients, their treatment options have remained essentially the same for decades, with cytotoxic chemotherapy providing only limited efficacy and considerable toxicity. The survival advantages seen with Dato-DXd may suggest a potential shift in the first-line treatment approach, offering clinicians a targeted option that may improve both disease control and patient outcomes.¹

Safety Profile and Ongoing Development

Dato-DXd’s safety profile in the TROPION-Breast02 study was consistent with previous clinical experience, with adverse effects being manageable and no new safety issues encountered. As with other ADCs, it is crucial to pay close attention to treatment-related toxicities. This is important now that Dato-DXd is being tested in different tumor types and treatment settings. Ongoing studies are further assessing the role of Dato-DXd in combination strategies and in other TROP2-expressing malignancies.²

Conclusion

The FDA’s priority review of Dato-DXd as a first-line therapy for metastatic TNBC patients who cannot receive immunotherapy is both a regulatory and a clinical breakthrough. By leveraging targeted ADC technology to deliver meaningful improvements in overall survival and disease control, DATROWAY has the potential to address a longstanding unmet need in this aggressive disease. If approved, DATROWAY could redefine the standard of care for a patient population with historically limited treatment options, marking an important advancement in the evolving landscape of TNBC therapy.^1,2

REFERENCES

1. DATROWAY® (datopotamab deruxtecan-dlnk) granted Priority Review in the US as 1st-line treatment for patients with metastatic triple-negative breast cancer who are not candidates for immunotherapy. AstraZeneca. Published February 3, 2026. Accessed February 3, 2026. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2026/DATROWAY-datopotamab-deruxtecan-dlnk-granted-Priority-Review-in-the-US-as-1st-line-treatment-for-patients-with-metastatic-triple-negative-breast-cancer-who-are-not-candidates-for-immunotherapy.html

2. Dent RA, Cescon DW, Bachelot T, et al. TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. Future Oncol. 2023;19(35):2349-2359. doi:10.2217/fon-2023-0228