The safety profile of Dato-DXd was consistent with what was shown in prior clinical trials evaluating the agent in patients with breast cancer. Data from TROPION-Breast02 will be shared with regulatory authorities and presented at an upcoming medical meeting, according to a news release from AstraZeneca.
“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,” Susan Galbraith, PhD, the executive vice president of oncology hematology research and development at AstraZeneca, stated in the news release. “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.”
What is Dato-DXd and in Which Disease Settings Is It FDA Approved?
Dato-DXd is a TROP2-directed antibody-drug conjugate (ADC) that holds indications from the FDA for the treatment of:
- Adult patients with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy.2
- Adult patients with unresectable or metastatic, hormone receptor (HR)–positive, HER2-negative (immunohistochemistry [IHC] 0, IHC 1+ or IHC 2+ /in situ hybridization–) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.3
What Are the Key Design Characteristics of TROPION-Breast02?
TROPION-Breast02 is an ongoing, open-label, multicenter international study that is examining Dato-DXd monotherapy for the treatment of adult patients with locally recurrent inoperable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy.4 Eligible patients must have received no prior chemotherapy or other systemic anticancer therapy for metastatic or locally recurrent inoperable breast cancer. Other inclusion criteria comprise at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, eligibility for at least 1 of the investigator-selected chemotherapy regimens, an adequate treatment washout period before day 1 of cycle 1, adequate organ function, and a life expectancy of at least 12 weeks.
Eligible patients were randomly assigned 1:1 to receive intravenous Dato-DXd or investigator’s choice of chemotherapy. Patients in the chemotherapy arm received capecitabine, carboplatin, or eribulin, or paclitaxel or nab-paclitaxel (Abraxane) if the patient had not received a prior taxane, or if a prior taxane had been given in the neoadjuvant/adjuvant setting with a disease-free interval of over 12 months.
The dual primary end points of the study are PFS per RECIST 1.1 criteria as assessed by blinded independent review committee and OS. Secondary end points include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to deterioration (TTD) in pain, TTD in physical functioning, TTD in breast and arm symptoms, TTD in global health status/quality of life, time to first subsequent therapy, time to second subsequent therapy, PFS2, pharmacokinetics, and safety.
“[Dato-DXd] the first ADC and the only therapy to significantly improve OS compared with chemotherapy in patients with metastatic TNBC for whom immunotherapy is not an option,” Ken Takeshita, MD, the global head of research and development at Daiichi Sankyo, added in the news release.1 “These landmark results from TROPION-Breast02 strengthen our confidence in our ongoing clinical development program for Dato-DXd in TNBC and other tumor types. We look forward to discussing these data with global regulatory authorities and to bringing Dato-DXd to patients with TNBC as soon as possible.”
References
- Datroway (datopotamab deruxtecan-dlnk) demonstrated statistically significant and clinically meaningful improvement in overall survival as 1st-line therapy for patients with metastatic triple-negative breast cancer for whom immunotherapy was not an option in TROPION-Breast02. News release. AstraZeneca. October 6, 2025. Accessed October 6, 2025. https://www.astrazeneca-us.com/media/press-releases/2025/DATROWAY-datopotamab-deruxtecan-dlnk-demonstrated-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-as-1st-line-therapy-for-patients-with-metastatic-triple-negative-breast-cancer-for-whom-immunotherapy-was-not-an-option-in-TROPION-Breast02.html
- FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. FDA. June 23, 2025. Accessed October 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-datopotamab-deruxtecan-dlnk-egfr-mutated-non-small-cell-lung-cancer
- FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. FDA. January 17, 2025. Accessed October 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast
- 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 10, 2025. Accessed October 6, 2025. https://clinicaltrials.gov/study/NCT05374512
