Datopotamab deruxtecan (Datroway; Dato-DXd) has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for use as monotherapy in the first-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.1
The decision, if granted, would address a substantial unmet need in approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy and have historically been limited to conventional cytotoxic chemotherapy in the first-line setting.
“TNBC remains one of the most aggressive types of breast cancer, with limited treatment options for patients with metastatic disease who are not candidates for immunotherapy and are currently treated with traditional chemotherapy,” John Tsai, MD, global head of Research and Development at Daiichi Sankyo, stated in a news release. “This positive recommendation by the CHMP underscores the potential for [Dato-DXd] to replace traditional chemotherapy in this setting and we look forward to working closely with the EMA to bring this new indication to patients in the European Union.”
The CHMP based its positive opinion on results from the phase 3 TROPION-Breast02 trial (NCT05374512), which met both of its primary efficacy end points.1,2 Primary results from the study, which were presented at the 2025 ESMO Congress, showed that the median PFS with Dato-DXd (n = 323) was 10.8 months (95% CI, 8.6-13.0) by blinded independent central review (BICR) vs 5.6 months (95% CI, 5.0-7.0) with investigator’s choice of chemotherapy (n = 321), translating to a 43% reduction in the risk of disease progression or death (HR, 0.57; 95% CI, 0.44-0.73; P < .0001).2 Moreover, the median OS with Dato-DXd was 23.7 months (95% CI, 19.8-25.6) vs 18.7 months (95% CI, 16.0-21.8) with ICC, translating to a 21% reduction in the risk of death (HR, 0.79; 95% CI, 0.64-0.98; P = .029).
Of note, Dato-DXd received FDA approval for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy in May 2026.3 Data from TROPION-Breast02 also supported this decision.
CHMP Recommends Dato-DXd for Approval
- The CHMP issued a positive opinion recommending Dato-DXd for European Union approval as first-line monotherapy in immunotherapy-ineligible unresectable or metastatic TNBC, based on dual primary end point results from the Tropion-Breast02 trial.
- Dato-DXd reduced the risk of death by 21% vs chemotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .029) and reduced the risk of progression or death by 43% (HR, 0.57; 95% CI, 0.44-0.73; P < .0001) in the trial population.
- The agent has already been approved in the United States, Brazil, and Russia for the same TNBC indication, with additional reviews ongoing in China, Japan, Australia, Canada, Singapore, and Switzerland under Project Orbis.
How was the Tropion-Breast02 trial designed?
The global, open-label, randomized study enrolled 644 patients with histologically or cytologically documented locally recurrent inoperable or metastatic TNBC who had not previously received chemotherapy or targeted systemic treatment in the locally recurrent inoperable or metastatic setting at sites across Africa, Asia, Europe, North America, and South America.1,2 Patients were also required to have an ECOG performance status of no greater than 1, and be ineligible or unable to receive immunotherapy.2 No minimum disease-free interval (DFI) was required.
Eligible 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, and carboplatin.2 Stratification factors included geographic region (US/Canada/Europe vs other regions), PD-L1 status (high vs low), and DFI (0-12 months vs ≥ 12 months). Treatment continued until progressive disease by investigator assessment and RECIST criteria, intolerable toxicity, or the meeting of other discontinuation criteria. Patients were permitted to receive subsequent treatment after disease progression or discontinuation.
The study’s dual primary end points were OS and PFS by BICR and RECIST 1.1 criteria. Secondary end points included PFS by investigator assessment, objective response rate (ORR), duration of response (DOR), disease control rate (DCR), pharmacokinetics, and safety.
What updated efficacy data were reported from TROPION-Breast02?
Beyond the dual primary end points, the trial demonstrated a notably higher ORR with Dato-DXd compared with chemotherapy.2 Dato-DXd elicited a confirmed ORR of 62.5% compared with 29.3% with the control.1 In the Dato-DXd arm, 9.0% of patients achieved a complete response (CR) as their best overall response, 54% of patients had a partial response, and 27% of patients had stable disease; 8% of patients experienced disease progression, and 2% of patients were not evaluable. The median DOR with Dato-DXd was 12.3 months (95% CI, 9.1-15.9) compared with 7.1 months (95% CI, 5.6-8.9) with chemotherapy.
Secondary end point data presented during the 2026 ASCO Annual Meeting also showed statistically significant improvements in time to first subsequent therapy or death, time to second progression or death, and time to second subsequent therapy or death with Dato-DXd vs investigator’s choice of chemotherapy.4
What is the safety profile of Dato-DXd in TNBC?
In TROPION-Breast02, any-grade treatment-related adverse effects (TRAEs) occurred in 93% of patients in the Dato-DXd arm (n = 319) vs 83% of those in the chemotherapy arm (n = 309). The incidence rates of grade 3 or higher TRAEs were 33% and 29%, respectively.2 Serious TRAEs occurred in 9% of those who received Dato-DXd and in 8% of those given chemotherapy. In the Dato-DXd arm, TRAEs led to dose interruption or reduction for 24% and 27% of patients and treatment discontinuation for 4% of patients; in the chemotherapy arm, TRAEs resulted in dose interruption, dose reduction, or treatment discontinuation in 19%, 18%, and 7% of patients, respectively.
References
- Datroway recommended for approval in the EU by CHMP as first-line treatment for patients with metastatic triple negative breast cancer who are not candidates for immunotherapy. News release. Daiichi Sankyo. June 26, 2026. Accessed June 26, 2026. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202606/20260626_E.pdf
- 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. Published online April 3, 2026. doi:10.1016/j.annonc.2026.03.008
- Datroway approved in the U.S. as first TROP2 directed antibody drug conjugate for first-line treatment of patients with metastatic triple negative breast cancer who are not PD-1/PD-L1 inhibitor candidates. News release. Daiichi Sankyo. May 22, 2026. Accessed June 26, 2026. https://daiichisankyo.us/web/dsi/press-releases/-/article/datroway-approved-in-the-us-as-first-trop2-directed-antibody-drug-conjugate-for-first-line-treatment-of-patients-with-metastatic-triple-negative-breast-cancer-who-are-not-pd-1pd-l1-inhibitor-candidates
- Cescon DW, Traina TA, 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: additional efficacy endpoints from the TROPION-Breast02 study. J Clin Oncol. 2026;44(suppl 16):1002. doi:10.1200/JCO.2026.44.16_suppl.1002
