The FDA has accepted and granted priority review to a supplemental biologics license application (sBLA) seeking the approval of datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) for the first-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not eligible to receive PD-1– or PD-L1–directed immunotherapy.1
The sBLA submission was supported by data from the phase 3 TROPION-Breast02 trial (NCT05374512), which were presented at the 2025 ESMO Congress.1,2 In this trial, treatment with Dato-DXd (n = 323) led to a 21% reduction in the risk of death (HR, 0.79; 95% CI, 0.64-0.98; P = .0291) and a 43% reduction in the risk of disease progression or death (HR, 0.57; 95% CI, 0.47-0.69; P < .0001) compared with investigator’s choice of chemotherapy (n = 321). The median overall survival (OS) was 23.7 months (95% CI, 19.8-25.6) with Dato-DXd compared with 18.7 months (95% CI, 16.0-21.8) with chemotherapy. The respective median progression-free survival (PFS) values by blinded independent central review were 10.8 months (95% CI, 8.6-13.0) and 5.6 months (95% CI, 5.0-7.0).
TROPION-Breast02 Trial of Dato-DXd in Immunotherapy-Ineligible TNBC: Highlights
- Dato-DXd significantly improved the median PFS to 10.8 months (95% CI, 8.6-13.0) compared with 5.6 months (95% CI, 5.0-7.0) with investigator’s choice of chemotherapy, representing a 43% reduction in the risk of disease progression or death (HR, 0.57; 95% CI, 0.47-0.69; P < .0001).
- The trial also demonstrated a statistically significant improvement in OS with Dato-DXd, with a median OS reaching 23.7 months (95% CI, 19.8-25.6) vs 18.7 months (95% CI, 16.0-21.8) with chemotherapy, reflecting a 21% reduction in the risk of death (HR, 0.79; 95% CI, 0.64-0.98; P = .0291).
- Dato-DXd generated a confirmed ORR of 62.5%, which was more than double the 29.3% ORR observed in the chemotherapy arm (OR, 4.24; 95% CI, 3.03-5.95).
Moreover, patients who received Dato-DXd achieved an overall response rate (ORR) of 62.5% vs 29.3% among those who received chemotherapy (odds ratio [OR], 4.24; 95% CI, 3.03-5.95). Furthermore, the median durations of response were 12.3 months (95% CI, 9.1-15.9) vs 7.1 months (95% CI, 5.6-8.9) in these respective populations.
The Prescription Drug User Fee Act target action date for the sBLA is planned for the second quarter of 2026.1
“[Dato-DXd] is the only medicine to significantly improve OS 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,” Susan Galbraith, executive vice president of Oncology Haematology R&D at AstraZeneca, stated in a news release. “The priority review of our submission underscores the [effect] 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.”
What is the design of the TROPION-Breast02 trial?
This open-label, global, randomized trial enrolled patients with histologically or cytologically confirmed locally recurrent unresectable or metastatic TNBC who had not received prior chemotherapy or targeted systemic therapy in the locally recurrent inoperable or metastatic setting.2 Patients needed to have an ECOG performance status of 0 or 1 and be ineligible to receive immunotherapy.
Patients were randomly assigned 1:1 to receive Dato-DXd at 6 mg/kg on day 1 every 3 weeks; or investigator’s choice of paclitaxel, nab-paclitaxel (Abraxane), capecitabine, eribulin mesylate/eribulin, or carboplatin.
What is the safety profile of Dato-DXd in metastatic TNBC?
TROPION-Breast02 investigators reported that the safety profile of Dato-DXd in this study was consistent with previous reports with the agent in patients with breast cancer. Among safety-evaluable patients in the Dato-DXd arm (n = 319), 93% experienced any-grade treatment-related adverse effects (TRAEs), and 33% had grade 3 or higher TRAEs. The most common any-grade TRAEs reported in this arm were dry eye (24%), stomatitis (57%), nausea (45%), constipation (23%), vomiting (20%), and decreased appetite (15%).
“[Dato-DXd] potentially could be the first medicine approved in the first-line setting to significantly extend OS and nearly double the time without disease progression or death compared with chemotherapy in patients with metastatic TNBC for whom immunotherapy was not an option,” Ken Takeshita, global head of R&D at Daiichi Sankyo, added in the news release.1 “We are eager to work with the FDA to bring this much-needed treatment option to patients with metastatic TNBC.”
References
- 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. News release. AstraZeneca. February 3, 2026. Accessed February 3, 2026. https://www.astrazeneca-us.com/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
- 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. Ann Oncol. 2025;36(suppl 2):S1566-S1567. doi:10.1016/j.annonc.2025.09.031
