AstraZeneca and Daiichi Sankyo Secure FDA Approval for Datroway in Frontline TNBC

The US Food and Drug Administration (FDA) has approved Datroway (datopotamab deruxtecan) for adults with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD‑1/PD‑L1 inhibitor therapy. The decision, granted under Priority Review and Project Orbis, marks the first frontline treatment advance beyond chemotherapy for the majority of metastatic TNBC patients unable to receive immunotherapy.

Patient Population

Approximately 70% of metastatic TNBC patients fall into this category due to PD‑L1–negative disease, prior immunotherapy exposure, comorbidities, or limited treatment access. Until now, chemotherapy remained the only standard option for these patients.

Trial Results: TROPION-Breast02

In the global Phase III TROPION‑Breast02 trial (NCT05374512) (n=644), Datroway demonstrated clear superiority over physician’s choice chemotherapy, which included paclitaxel, nab‑paclitaxel, capecitabine, carboplatin, or eribulin. Patients treated with Datroway achieved a median progression‑free survival of 10.8 months compared with 5.6 months for chemotherapy (HR 0.57; p<0.0001). Median overall survival was also extended, reaching 23.7 months versus 18.7 months (HR 0.79; p=0.0290).

The antibody‑drug conjugate produced an objective response rate of 64% compared with 30% for chemotherapy, with responses lasting a median of 12.3 months. These results establish Datroway as the first therapy to significantly improve both progression‑free and overall survival in the frontline metastatic TNBC setting for patients ineligible for immunotherapy.

Safety Profile

Safety findings were consistent with prior Datroway studies. Common adverse events included stomatitis and ocular events, manageable with supportive care. Interstitial lung disease (ILD) was rare, with one grade 5 case reported. Grade ≥3 treatment-related adverse events occurred in approximately 33% of patients, with a 4% discontinuation rate.

Opinion

Tiffany Traina, MD, of Memorial Sloan Kettering Cancer Center, emphasized that Datroway is the first medicine to significantly prolong overall survival in the first-line metastatic TNBC setting for patients ineligible for immunotherapy. Company executives underscored the therapy’s potential to reshape frontline standards across aggressive breast cancer subtypes.

Mechanism of Action

Datroway is a TROP2-directed antibody-drug conjugate (ADC) built on Daiichi Sankyo’s DXd platform. It links a humanized anti‑TROP2 monoclonal antibody to a topoisomerase I inhibitor payload via a cleavable linker. TROP2 is widely expressed in TNBC and associated with aggressive tumor biology and poor survival outcomes.

Regulatory and Guideline Impact

The FDA reviewed the application under Project Orbis, enabling parallel regulatory assessments in Australia, Canada, Singapore, Switzerland, the European Union, China, and Japan. Datroway has also been incorporated into the NCCN Guidelines as a Category 1 preferred first-line treatment option for metastatic TNBC patients ineligible for immunotherapy.

Expanding Clinical Footprint

Datroway now holds three US indications, including two in breast cancer, highlighting its expanding role in oncology. The approval represents a pivotal advance for a patient population historically underserved by immunotherapy, positioning Datroway as a new global standard in frontline TNBC care.

 Reference

Datroway approved in the US as first TROP2-directed antibody drug conjugate for 1st-line treatment of patients with metastatic triple-negative breast cancer who are not PD-1/PD-L1 inhibitor candidates

Study Details | NCT05374512 | A Study of Dato-DXd Versus Investigator’s Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (TROPION-Breast02) | ClinicalTrials.gov