Daiichi Sankyo announced that China’s National Medical Products Administration (NMPA) has approved datopotamab deruxtecan for adults with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.
The approval is based on results from the Phase 3 TROPION-Breast02 trial, which demonstrated statistically significant improvements in overall survival and progression-free survival compared with investigator’s choice of chemotherapy. The findings were presented at the European Society for Medical Oncology Congress in 2025 and subsequently published in Annals of Oncology, according to the Daiichi Sankyo press release.
Datopotamab deruxtecan is a TROP2-directed antibody-drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca. The decision brings its number of approved breast cancer indications in China to two.
Zhimin Shao, Director, Fudan University Cancer Institute and Breast Cancer, China, and lead investigator in China of the TROPION-Breast02 trial, highlighted the challenges of treating patients with newly diagnosed metastatic TNBC who are not candidates for immunotherapy:
“One of the greatest challenges in my clinical practice is treating patients at their first metastatic triple negative breast cancer diagnosis who are not candidates for immunotherapy since there has been limited treatment options available.”
Commenting on the approval of datopotamab deruxtecan in China, Shao said it introduces an important new treatment option supported by clinically meaningful improvements in overall survival and progression-free survival. He described the approval as a significant advancement over the current standard of care.
TROPION-Breast02 Overall Survival and Progression-Free Survival Results
In TROPION-Breast02, median overall survival was 23.7 months with datopotamab deruxtecan versus 18.7 months with chemotherapy, representing a statistically significant improvement of 5.0 months. The hazard ratio for overall survival was 0.79, with a 95% confidence interval of 0.64–0.98 and a p-value of 0.0291.
Datopotamab deruxtecan also reduced the risk of disease progression or death by 43% compared with chemotherapy, as assessed by blinded independent central review. Median progression-free survival was 10.8 months versus 5.6 months, respectively, with a hazard ratio of 0.57 (95% CI, 0.47–0.69; p<0.0001).
The objective response rate was 63% with datopotamab deruxtecan compared with 29% with chemotherapy.
Trial Design and Patient Population
TROPION-Breast02 is a global, multicenter, randomized, open-label Phase 3 trial evaluating datopotamab deruxtecan against investigator’s choice of chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option.
Chemotherapy options included paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin. The study included patients whose tumors did not express PD-L1, as well as those with PD-L1-expressing tumors who could not receive immunotherapy because of prior exposure in early-stage disease, comorbidities or lack of access in their geographic region.
Patients with newly diagnosed metastatic disease or recurrent disease were eligible regardless of their disease-free interval. Enrollment also included patients with poor prognostic factors, such as stable brain metastases.
A total of 644 patients were enrolled at sites across Africa, Asia, Europe, North America and South America. The dual primary endpoints were overall survival and progression-free survival assessed by blinded independent central review. Secondary endpoints included investigator-assessed progression-free survival, objective response rate, duration of response, disease control rate, pharmacokinetics, and safety.
Safety Findings
The safety profile of datopotamab deruxtecan at 6 mg/kg was evaluated in 319 patients with TNBC who received the treatment in TROPION-Breast02.
Adverse reactions, including laboratory abnormalities, reported in at least 20% of patients included stomatitis, increased amylase, nausea, alopecia, decreased hemoglobin, decreased white blood cells, constipation, decreased calcium and fatigue.
Other commonly reported reactions or laboratory abnormalities included decreased lymphocytes, decreased neutrophils, increased alanine aminotransferase, increased aspartate aminotransferase, dry eye, decreased albumin, vomiting, decreased sodium and increased blood alkaline phosphatase.
Serious adverse reactions occurred in 5.6% of patients. Vomiting and anemia were the serious adverse reactions reported in more than 1% of patients. One patient fatality was attributed to interstitial lung disease/pneumonitis.
Triple-Negative Breast Cancer in China
According to the release, TNBC accounts for approximately 15% of breast cancer cases, with an estimated 365,000 diagnoses worldwide each year, including approximately 56,000 in China.
TNBC is defined by the absence of estrogen receptors, progesterone receptors and HER2 overexpression. It is diagnosed more frequently in younger and premenopausal women.
The release reports that approximately 70% of patients with metastatic TNBC are not candidates for immunotherapy, a population for whom chemotherapy was the standard first-line treatment. Reasons for immunotherapy ineligibility can include tumor characteristics, prior treatment, comorbidities and treatment accessibility.
Michio Hayashi, China President of Daiichi Sankyo, noted that datopotamab deruxtecan is the only TROP2-directed antibody-drug conjugate approved in China with an overall survival benefit in this setting, according to the company.
Mary Guan, General Manager of China Oncology Business at AstraZeneca, said:
“There remains a critical need for innovative treatment options that can help improve outcomes based on the aggressive nature of triple negative breast cancer.”
Datopotamab Deruxtecan Approvals and Development
Datopotamab deruxtecan consists of a humanized anti-TROP2 monoclonal antibody linked to topoisomerase I inhibitor payloads through cleavable linkers. TROP2 is a protein expressed in several solid tumors, including TNBC.
According to the release, datopotamab deruxtecan is approved in more than 35 countries and regions, including China, the European Union, Japan and the United States, for adults with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy. Additional reviews are underway in Australia, Canada, Israel and Switzerland through Project Orbis.
The medicine is also approved in more than 45 countries and regions for adults with unresectable or metastatic hormone receptor-positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease, based on TROPION-Breast01.
Its global clinical development program includes more than 20 trials across multiple cancers, including non-small cell lung cancer, triple-negative breast cancer and urothelial cancer. These studies are evaluating datopotamab deruxtecan alone and in combination with other treatments across different disease settings.
You can also read: Trastuzumab Deruxtecan Approved in China for HER2-Positive Early Breast Cancer With Residual Disease.
