FDA Grants Priority Review to Dato-DXd First-Line Metastatic TNBC

The FDA has accepted and granted priority review to the supplemental biologics license application (sBLA) for datopotamab deruxtecan (Dato-DXd; Datroway) for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC). The designation specifically applies to patients who are not candidates for PD-1 or PD-L1 inhibitor therapy.¹

The sBLA is supported by results from the pivotal phase 3 TROPION-Breast02 clinical trial (NCT05374512), which evaluated the efficacy and safety of Dato-DXd compared with the investigator’s choice of chemotherapy in the first-line setting. Under the Prescription Drug User Fee Act, the target action date is expected in Q2 of 2026.

“[Dato-DXd] is the only medicine to significantly improve overall survival compared [with] chemotherapy in this patient population as demonstrated in the TROPION-Breast02 trial—the results of which are even more striking considering the trial enrolled a subset of patients with highly aggressive disease. The priority review of our submission underscores the impact of these results and its review under Project Orbis signals a widely shared commitment to bringing [Dato-DXd] to patients around the world as quickly as possible,” said Susan Galbraith, executive vice president of Oncology Hematology Research and Development at AstraZeneca, in a news release.

Survival Outcomes and Efficacy

In the TROPION-Breast02 study, Dato-DXd demonstrated a statistically significant and clinically meaningful improvement in the dual primary end points of overall survival (OS) and progression-free survival (PFS). Analysis revealed a median OS of 23.7 months for patients receiving the antibody-drug conjugate (ADC) compared with 18.7 months for those in the chemotherapy cohort (HR 0.79; 95% CI: 0.64-0.98; P =.0291). This 5.0-month improvement represents a landmark in the management of metastatic TNBC, a subtype historically characterized by poor prognosis and limited therapeutic options.^1,2

Furthermore, Dato-DXd reduced the risk of disease progression or death by 43% compared with chemotherapy (HR 0.57; 95% CI: 0.47-0.69; P <.0001). The median PFS was 10.8 months in the experimental arm vs 5.6 months in the control arm. Secondary end points also favored the ADC, with an objective response rate (ORR) of 62.5% and a median duration of response (DOR) of 12.3 months, compared with an ORR of 29.3% and a DOR of 7.1 months for chemotherapy.

Addressing an Unmet Need

TNBC accounts for approximately 15% of all breast cancer cases.¹ While immunotherapy in combination with chemotherapy has improved outcomes for patients with PD-L1–expressing tumors, nearly 70% of patients with metastatic disease are not eligible for currently approved immune checkpoint inhibitor regimens. For this population, single-agent chemotherapy has remained the standard of care despite its modest efficacy.

Dato-DXd is a TROP2-directed ADC utilizing a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload. TROP2 is a transmembrane glycoprotein overexpressed most TNBC cases, making it a viable therapeutic target.

Safety and Regulatory Timeline

The safety profile of Dato-DXd in TROPION-Breast02 was consistent with previous trials. Grade 3 or higher treatment-related adverse events occurred in 32% of patients. Notable toxicities associated with the DXd-based ADC platform include stomatitis and ocular events, as well as a risk of interstitial lung disease (ILD)/pneumonitis. Clinicians are advised to monitor for new or worsening respiratory symptoms, as early detection and management of ILD are critical.

REFERENCES

1. Datroway granted priority review in the US as 1st-line treatment for patients with metastatic triple-negative breast cancer who are not candidates for immunotherapy. News release. AstraZeneca. February 3, 2026. Accessed February 3, 2026. https://tinyurl.com/48fyu5tt

2. Dent R, et al. Datopotamab deruxtecan vs chemotherapy in first-line metastatic triple-negative breast cancer: Results from the Phase 3 TROPION-Breast02 study. Presented at: ESMO Congress 2025; September 2025; Berlin, Germany. Abstract LBA21.