Dato-DXd Delivers Significant TNBC Survival Benefits in Phase 3 Trial

The antibody-drug conjugate (ADC) datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) has demonstrated statistically significant improvements in overall survival (OS) and progression-free survival (PFS) compared with chemotherapy in first-line treatment of patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option.¹

These positive primary end point results were derived from the pivotal phase 3 TROPION-Breast02 trial (NCT05374512) and suggest meaningful clinical benefit in an aggressive, difficult-to-treat cancer with poor prognosis and limited targeted therapy options.^2,3 The data, along with safety data which revealed a safety profile consistent with previous trials evaluating the agent, will be presented at an upcoming medical meeting, according to the sponsors, AstraZeneca and Daiichi Sankyo.¹

“TROPION-Breast02 is the only trial ever to show an [OS] benefit in the first-line treatment of patients with metastatic [TNBC] for whom immunotherapy is not an option. We expect today’s results will mark an inflection point in the treatment of these patients who have the poorest prognosis of any type of breast cancer and urgently need better options,” Susan Galbraith, PhD, MB BChir, executive vice president of oncology research and development at AstraZeneca, said in a news release.¹

Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, added, “We look forward to discussing these data with global regulatory authorities and to bringing [Dato-DXd] to patients with [TNBC] as soon as possible."¹

What Is the Background of the TROPION-Breast02 Trial?

TROPION-Breast02 is a randomized, open-label, global, multicenter study assessing the efficacy and safety of Dato-DXd vs standard-of-care chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic TNBC.⁴ Dato-DXd is an investigational TROP2-directed DXd ADC comprised of a humanized monoclonal antibody linked to a topoisomerase I inhibitor via a cleavable linker.

The study’s primary objective is to demonstrate superiority of the agent compared with first-line chemotherapy in the dual primary end points of OS and PFS. Secondary end points examined include objective response rate, duration of response, disease control rate, safety, pharmacokinetics, time to deterioration, time to first and second subsequent therapies, and immunogenicity.

The study enrolled 644 adult patients with TNBC across 227 locations in Africa, Asia, North America, and South America for whom immunotherapy was not an option due to a lack of PD-L1–expressing tumors. Patients were randomly assigned 1:1 to receive either intravenous Dato-DXd 6 mg/kg every 3 weeks or investigator’s choice of chemotherapy.²

Enrollment and dosing for the trial began in 2022, with an estimated completion date projected for December 2025.

What Are the Other Studied Indications for Dato-DXd?

Dato-DXd in TNBC is being investigated in 3 other phase 3 clinical trials: TROPION-Breast03 (NCT05629585) for stage I to III TNBC with residual invasive disease following neoadjuvant systemic therapy; TROPION-Breast04 (NCT06112379) in combination with durvalumab (Imfinzi) for stage II to III TNBC or hormone receptor (HR)–low, HER2-low, or HER2-negative breast cancer; and TROPION-Breast05 (NCT06103864) with or without durvalumab for metastatic TNBC with PD-L1–expressing tumors.

Previously, the phase 3 TROPION-Breast01 study (NCT05104866) evaluating the agent in HR-positive, HER2-low or -negative breast cancer met its primary end point of PFS, but failed to meet significance in its other primary end point of OS.⁵ Earlier in 2025, the FDA granted accelerated approval to Dato-DXd for previously treated, locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC).⁶

REFERENCES:

1. Datroway (datopotamab deruxtecan-dlnk) improved OS and PFS in TROPION-Breast02. News release. Business Wire. October 6, 2025. Accessed October 6, 2025. https://tinyurl.com/bdzx4xss

2. Dent RA, Cescon DW, Bachelot T, et al. TROPION-Breast02: datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. Future Oncol. 2023;19(35):2349-2359. doi:10.2217/fon-2023-0228

3. Bianchini G, Balko JM, Mayer IA, et al. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin ncol. 2016;13(11):674-690. doi:10.1038/nrclinonc.2016.66

4. 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 July 7, 2025. Accessed October 6, 2025. https://clinicaltrials.gov/study/NCT05374512

5. Datopotamab deruxtecan significantly extended progression-free survival vs. chemotherapy in patients with HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 phase III trial. News release. AstraZeneca. October 23, 2023. Accessed October 24, 2023. https://tinyurl.com/bd658nse

6. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. News release. US FDA. June 23, 2025. Accessed June 23, 2025. https://tinyurl.com/mu5spftb