Tokyo, Japan, November 12, 2026
Daiichi Sankyo has submitted a supplemental New Drug Application (sNDA) in Japan for Enhertu® (trastuzumab deruxtecan) for patients with HER2-expressing advanced or recurrent uterine carcinosarcoma. The application has been submitted to Japan’s Ministry of Health, Labour and Welfare (MHLW) and seeks to expand the treatment options available for patients with this rare and aggressive form of uterine cancer. The submission covers tumors expressing HER2 at immunohistochemistry (IHC) levels of 3+, 2+ or 1+ and is supported by findings from the Japanese Phase 2 STATICE clinical trial. The study demonstrated durable responses in patients whose disease had progressed or returned after previous chemotherapy. Daiichi Sankyo describes Enhertu as the first HER2-directed medicine to demonstrate clinical activity in this patient population in Japan. The regulatory submission represents an important development in targeted treatment research for uterine carcinosarcoma, where therapeutic options remain limited, particularly after disease recurrence.
STATICE Phase 2 Trial Supports Regulatory Submission
The sNDA is based on results from STATICE, a multicenter, open-label, single-arm, investigator-initiated Phase 2 trial conducted in Japan. The study evaluated Enhertu in patients with HER2-expressing advanced or recurrent uterine carcinosarcoma who had previously received chemotherapy, including adjuvant chemotherapy. A total of 34 patients were enrolled across seven clinical sites. The trial investigated two dose levels, 6.4 mg/kg and 5.4 mg/kg, administered intravenously. During the study, the dose was modified from 6.4 mg/kg to 5.4 mg/kg following an assessment of the risk-benefit profile, with the lower dose subsequently identified as the preferred dose for this patient population. The primary endpoint was objective response rate (ORR) assessed through central review in patients whose tumors had HER2 expression of IHC 2+ or higher. Secondary endpoints included investigator-assessed response rates, response rates in patients with IHC 1+ tumors, progression-free survival, overall survival and safety. The trial demonstrated durable responses across different levels of HER2 expression. Its findings were published in the Journal of Clinical Oncology. Importantly, STATICE was the first prospective clinical trial to demonstrate activity of a HER2-directed medicine in this rare cancer type, providing clinical evidence supporting further development of targeted treatment strategies.
Enhertu Targets HER2 Through Antibody-Drug Conjugate Technology
Enhertu (trastuzumab deruxtecan) is a specifically engineered HER2-directed antibody-drug conjugate (ADC) discovered by Daiichi Sankyo. It combines a monoclonal antibody that recognizes HER2 with a cytotoxic payload called DXd, a topoisomerase I inhibitor derivative, through a cleavable linker. This design enables the medicine to deliver its anticancer payload to cells expressing the HER2 target. HER2 is a receptor protein involved in cell growth and differentiation and is expressed in several tumor types. In uterine carcinosarcoma, HER2 expression has been identified as a potential therapeutic target, with the company citing research indicating that approximately 72.3% of patients may have tumors expressing HER2 at IHC 1+, 2+ or 3+ levels. Uterine carcinosarcoma is a rare and highly aggressive form of endometrial cancer, accounting for fewer than 5% of endometrial cancer cases in Japan. Despite its relatively low incidence, it contributes disproportionately to endometrial cancer-related deaths. Treatment commonly involves surgery and chemotherapy, including paclitaxel plus carboplatin for unresectable advanced or recurrent disease. However, recurrence remains a significant challenge, highlighting the need for additional treatment approaches. Enhertu is already approved in Japan for certain patients with HER2-positive uterine carcinosarcoma when standard treatment is not appropriate; the new application seeks an indication covering the broader HER2-expressing population described in the submission.
Advertisement
Japan Review Could Expand Targeted Treatment Options
Daiichi Sankyo stated that the submission reflects the potential value of targeting HER2 in patients with difficult-to-treat uterine carcinosarcoma. Yuki Abe, PhD, Senior Executive Officer and Head of the R&D Division in Japan, emphasized the durable activity observed in STATICE and the potential for Enhertu to provide an additional targeted treatment option if approved. The company is responsible for developing and commercializing Enhertu in Japan, while it collaborates globally with AstraZeneca on the medicine’s development and commercialization outside Japan. Enhertu is already approved in more than 50 countries and regions for certain patients with HER2-positive solid tumors who have received prior treatment or have no satisfactory alternative treatment options. The Japanese sNDA now places the uterine carcinosarcoma indication under regulatory review for the specified HER2-expressing population. The submission is not an approval, and the MHLW will need to complete its assessment before any expanded indication can be authorized. If approved, the expanded use could provide an additional targeted treatment option for eligible patients with advanced or recurrent uterine carcinosarcoma in Japan.
Source: Daiichi Sankyo press release
