On October 6, 2025 Astrazeneca reported positive high-level results from the TROPION-Breast02 Phase III trial showed Datroway (datopotamab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement for the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to investigator’s choice of chemotherapy as 1st-line treatment for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) for whom immunotherapy was not an option (Press release, AstraZeneca, OCT 6, 2025, View Source [SID1234656455]).
Approximately 70% of patients with metastatic TNBC are not candidates for immunotherapy, including all patients whose tumours do not express PD-L1 as well as patients with PD-L1 expressing tumours who cannot receive immunotherapy due to other factors.1 Chemotherapy remains the 1st-line standard of care for these patients.2
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "TROPION-Breast02 is the only trial ever to show an overall survival benefit in the first-line treatment of patients with metastatic triple-negative breast cancer 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."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "Datroway is the first antibody drug conjugate and the only therapy to significantly improve overall survival compared to chemotherapy in patients with metastatic triple-negative breast cancer for whom immunotherapy is not an option. These landmark results from TROPION-Breast02 strengthen our confidence in our ongoing clinical development programme for Datroway in triple-negative breast cancer and other tumour types. We look forward to discussing these data with global regulatory authorities and to bringing Datroway to patients with triple-negative breast cancer as soon as possible."
The safety profile of Datroway was consistent with previous clinical trials of Datroway in breast cancer. These data will be presented at an upcoming medical meeting and shared with regulatory authorities.
Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
AstraZeneca and Daiichi Sankyo are evaluating Datroway across stages and treatment settings of TNBC in three additional Phase III trials. TROPION-Breast03 is evaluating Datroway with or without Imfinzi (durvalumab) in patients with Stage I-III TNBC with residual invasive disease after neoadjuvant systemic therapy. TROPION-Breast04 is evaluating neoadjuvant Datroway plus Imfinzi in patients with Stage II-III triple-negative or hormone receptor (HR)-low, HER2-low or -negative breast cancer. TROPION-Breast05 is evaluating 1st-line Datroway with or without Imfinzi in patients with metastatic TNBC whose tumours express PD-L1.
Notes
Triple-negative breast cancer
TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.3,4 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.5-7 Metastatic TNBC is the most aggressive type of breast cancer and has the worst prognosis, with median overall survival of just 12 to 18 months and only about 14% of patients living five years following diagnosis.5,8,9
While some breast cancers may test positive for oestrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.5 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.5 For patients with metastatic disease with PD-L1 expressing tumours, the addition of immunotherapy to chemotherapy has improved outcomes in the 1st-line setting.10,11 However, for the approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, chemotherapy remains the 1st-line standard of care.1,2
TROP2 is a protein broadly expressed in several solid tumours including TNBC.12 TROP2 is associated with increased tumour progression and poor survival in patients with breast cancer.13,14
TROPION-Breast02
TROPION-Breast02 is a global, multicentre, randomised, open-label Phase III trial evaluating the efficacy and safety of Datroway versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumours did not express PD-L1 as well as patients with PD-L1 expressing tumours who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrolment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as brain metastases.
The dual primary endpoints of TROPION-Breast02 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response, disease control rate, pharmacokinetics and safety.
TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America. For more information, visit ClinicalTrials.gov.
Datroway
Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the US only) is a TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Datroway is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Datroway is approved in more than 35 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on results from the TROPION-Breast01 trial.
Datroway is available in the US under accelerated approval 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 based on results from the TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial. Datroway is approved in Russia for the same population.
Datroway clinical development programme
A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of Datroway across multiple cancers, including NSCLC, TNBC and urothelial cancer. The programme includes eight Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating Datroway as a monotherapy and in combination with other anticancer treatments in various settings.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!