Dato-DXd Receives FDA Approval for Unresectable or Metastatic TNBC

The FDA has approved datopotamab deruxtecan-dlnk (Dato-DXd, Datroway; Daiichi Sankyo, Inc) for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy. Approval is supported by data from the phase 3 TROPION-Breast02 trial (NCT05374512).^1,2

What are ADCs and Dato-DXd?

Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic strategy in oncology, delivering 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 therapeutic need in patients with metastatic TNBC. Its target, TROP2, is a transmembrane glycoprotein highly expressed across TNBC tumors, making it an attractive therapeutic target.³

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. On February 3, 2026, Dato-DXd’s supplemental biologics license application for unresectable or metastatic TNBC received a priority review by the FDA.³

TROPION-Breast02 Clinical Trial

TROPION-Breast02 is a randomized, open-label trial that enrolled 644 patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. They were randomly assigned to receive Dato-DXd (n = 323; 6 mg/kg administered intravenously every 3 weeks) or investigator’s choice of chemotherapy (n = 321). Randomization was stratified by geographic location, disease-free interval, and PD-L1 status.^1,2

Dual primary end points were progression-free survival (PFS) and overall survival (OS), and efficacy analyses were performed in the intention-to-treat population. Safety analyses included all patients who received at least 1 dose of study treatment. Results were published in Annals of Oncology.^2,4

According to the data, median PFS was 10.8 months (95% CI, 8.6-13.0) with Dato-DXd and 5.6 months (95% CI, 5.0-7.0) with chemotherapy (HR, 0.57; 99% CI, 0.44-0.73; P < .0001). Median OS was 23.7 months (95% CI, 19.8-25.6) with Dato-DXd and 18.7 months (95% CI, 16.0-21.8) with chemotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .029). The confirmed overall response rate (ORR) was approximately 64% (95% CI, 58%-69%) and 30% (95% CI, 25%-36%) in these respective arms.⁴

In the TROPION-Breast02 trial, treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 105 (33%) patients who received Dato-DXd and in 89 (29%) patients who received chemotherapy, respectively. TRAEs that led to treatment discontinuation occurred in 14 (4%) and 23 (7%) patients in these respective groups. No deaths occurred in either arm.⁴

The recommended Dato-DXd dose is 6 mg/kg (up to a maximum of 540 mg for patients weighing ≥ 90 kg), administered as an intravenous infusion once every 3 weeks (21-day cycle), until disease progression or unacceptable toxicity.¹

The Pharmacist’s Role

Pharmacists play an increasingly important role in the management of TNBC as newer therapies such as ADCs and immunotherapy combinations continue to emerge. Pharmacists should understand the mechanism of action, place in therapy, and evolving clinical evidence surrounding agents of Dato-DXd. Familiarity with key efficacy outcomes—including ORRs, PFS, and patient selection criteria such as PD-L1 positivity—is essential to helping oncology teams interpret data and optimize treatment decisions as new evidence becomes available.

In clinical practice, pharmacists are central to toxicity monitoring, patient counseling, and supportive care management. Because ADCs can carry distinct AE profiles, pharmacists should be prepared to identify and manage toxicities and hematologic effects, as well as immune-related AEs when therapies are combined with immunotherapy.

Through patient education, regimen optimization, and collaboration with multidisciplinary oncology teams, pharmacists help ensure the safe and effective implementation of complex treatment strategies while supporting adherence and quality of care.

REFERENCES

1. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic triple-negative breast cancer. FDA. May 22, 2026. Accessed May 22, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-triple-negative-breast-cancer

2. 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. Updated May 15, 2026. Accessed May 22, 2026. https://clinicaltrials.gov/study/NCT05374512

3. Valletti D. Dato-DXd granted priority review as first-line therapy for metastatic triple-negative breast cancer. Pharmacy Times. February 3, 2026. Accessed May 22, 2026. https://www.pharmacytimes.com/view/dato-dxd-granted-priority-review-as-first-line-therapy-for-metastatic-triple-negative-breast-cancer

4. Dent R, Shao Z, Schmid P, et al. Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial. Ann Oncol. 2026:S0923-7534(26)00130-4. doi:10.1016/j.annonc.2026.03.008