Dato-DXd Earns Priority Review in Unresectable/Metastatic TNBC

The FDA has accepted and granted priority review to a supplemental biologics license for datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) for the treatment of patients with unresectable or metastatic triple-negative breast cancer who are ineligible for treatment with a PD-1/PD-L1 inhibitor, according to a news release from AstraZeneca.¹

This decision was based on results from the phase 3 TROPION-Breast02 trial (NCT05374512).² A Prescription Drug User Fee Act date has been set for the second quarter 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,” Susan Galbraith, executive vice president, Oncology Hematology Research and Development, AstraZeneca, said in the press release.

Efficacy results were presented at the European Society for Medical Oncology Congress 2025. The median progression-free survival (PFS) was 10.8 months (95% CI, 8.6-13.0) via investigator’s choice of chemotherapy vs 5.6 months (95% CI, 5.0-7.0) for investigator’s choice of chemotherapy; with a 43% reduction in disease progression or death (HR, 0.57; 95% CI, 0.47-0.69; P <.0001).

Additionally, the median overall survival (OS) was 23.7 months (95% CI, 19.8-25.6) in the Dato-DXd arm vs 18.7 months (95% CI, 16.0-21.8) in the chemotherapy arm; this showed a 21% reduction in the risk of death (HR, 0.79; 95% CI, 0.60-0.98; P = .0291). At 12 and 18 months, the OS rates were 75.2% vs 67.8% and 61.2% vs 51.3%, respectively.

The investigator-assessed PFS was 9.6 months (95% CI, 7.4-11.2) in the Dato-DXd arm vs 5.2 months (95% CI, 4.2-5.6) in the chemotherapy arm and was consistent with blinded independent central review (HR, 0.56; 95% CI, 0.47-0.67). The 12- and 18-months rates were 40.7% vs 18.5% and 27.5% vs 9.2%, respectively.

The objective response rate (ORR) was 62.5% vs 29.3%, between each arm. This demonstrated a 33.2% difference (OR, 4.24; 95% CI, 3.03-5.95). A complete response was achieved by 9.0% of patients as their best overall response, 53.6% had partial responses, and 26.9% had stable disease. Additionally, 8.4% of patients experienced disease progression and 2.2% were not evaluable for response. The median duration of response (DOR) was 12.3 months (95% CI, 9.1-15.9) compared with 7.1 months (95% CI, 5.6-8.9).

“[The trial] met both dual primary end points, [with] first-line Dato-DXd demonstrating statistically significant and clinically meaningful improvement in OS and PFS over [investigator’s choice of chemotherapy]. TROPION-Breast02 results support Data-DXd as the new first-line standard of care for patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy is not an option.” Rebecca Dent, MD, MSc, head of the department of Medical Oncology at the National Cancer Center Singapore at SingHealth, said during the presentation of the data.

The TROPION-Breast02 trial randomly assigned patients 1:1 to either receive Dato-DXd at 6 mg/kg on day 1 every 3 weeks (n = 323) or investigator’s choice of chemotherapy (n = 321). The dual primary end points were PFS and OS. Key secondary end points included investigator-assessed PFS, ORR, DOR, and safety.

The most common treatment-related adverse effects (TRAEs) in the Dato-DXd arm were dry eye (any grade, 24%; grade ≥3, 1%), stomatitis (57%; 8%), nausea (45%; <1%), constipation (23%; <1%), vomiting (20%; 1%), and decreased appetite (15%; <1%). TRAEs of special interest were oral mucositis or stomatitis (grade 1, 24%; grade 2, 27%; grade ≥3, 8%).

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. February 3, 2026. https://tinyurl.com/2mp7h466
2. Dent RA, Shao Z, Schmid P, et al. First-line datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option: primary results from the randomised, phase 3 TROPION-Breast02 trial. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA21.