On October 7, 2025 Daiichi Sankyo (TSE: 4568) reported it has submitted a supplemental New Drug Application (sNDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) for ENHERTU (trastuzumab deruxtecan) in combination with pertuzumab for the treatment of patients with HER2 positive unresectable or recurrent breast cancer.
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ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being developed and commercialized by Daiichi Sankyo in Japan.
HER2 targeted therapies have improved outcomes in HER2 positive metastatic breast cancer; however, prognosis remains poor with most patients experiencing disease progression within two years of first-line treatment with taxane, trastuzumab and pertuzumab (THP), which has been the standard of care for more than a decade.
The sNDA is based on data from the DESTINY-Breast09 phase 3 trial presented during a special latebreaking oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO25) Annual Meeting.
"In DESTINY-Breast09, ENHERTU plus pertuzumab demonstrated a median progression-free survival of more than three years, which represents an impressive improvement over the current standard of care," said Yuki Abe, PhD, Head of R&D Division in Japan and Head of Research, Daiichi Sankyo. "Following the recent approval of ENHERTU in Japan for the treatment of HER2 low or HER2 ultralow metastatic breast cancer, this new submission of ENHERTU plus pertuzumab for the first-line treatment of patients with HER2 positive disease underscores the commitment of Daiichi Sankyo to bring ENHERTU to as many patients as possible in this region across certain subtypes of metastatic breast cancer."
A supplemental Biologics License Application for ENHERTU plus pertuzumab based on data from DESTINY-Breast09 was granted Priority Review in the U.S. under the Real-Time Oncology Review program. The Priority Review follows receipt of Breakthrough Therapy Designation granted by the FDA in July 2025.
About DESTINY-Breast09
DESTINY-Breast09 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP (a taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab) as a first-line treatment in patients with HER2 positive metastatic breast cancer.
Patients were randomized 1:1:1 to receive either ENHERTU monotherapy with a pertuzumab matching placebo; ENHERTU in combination with pertuzumab; or THP. Randomization was stratified by prior treatment (de novo metastatic disease versus progression from early-stage disease), hormone receptor (HR) status and PIK3CA mutation status.
The primary endpoint of DESTINY-Breast09 is progression-free survival (PFS) as assessed by blinded independent central review in both the ENHERTU monotherapy and ENHERTU combination arms. Secondary endpoints include investigator-assessed PFS, overall survival, objective response rate, duration of response, pharmacokinetics and safety. The investigational arm assessing ENHERTU monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.
DESTINY-Breast09 enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, North America, and South America. For more information about the trial, visit ClinicalTrials.gov.
About HER2 Positive Metastatic Breast Cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.5 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.5 In Japan, breast cancer is the most common cancer in women, with approximately 92,000 cases of breast cancer diagnosed and 17,600 deaths in 2022. 6 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or progress to metastatic disease are expected to live five years following diagnosis.
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast cancer.8 HER2 protein overexpression may occur as a result of HER2 gene amplification.1 Approximately one in five cases of breast cancer are considered HER2 positive.9 3 HER2 positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2 that affects 15% to 20% of patients with metastatic breast cancer.10 While HER2 targeted therapies have improved outcomes, prognosis remains poor with most patients experiencing disease progression within two years of first-line treatment with THP, which has been the standard of care for more than a decade.1,2,3,4 Further, approximately 25% to 30% of patients do not receive any treatment following first-line therapy due to discontinuation or death.
About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
ENHERTU (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
ENHERTU (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
ENHERTU (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.
ENHERTU (5.4 mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
ENHERTU (6.4 mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
ENHERTU (5.4 mg/kg) is approved in more than 10 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
About the ENHERTU Clinical Development Program
A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2 targetable cancers.
(Press release, Daiichi Sankyo, OCT 7, 2025, View Source [SID1234665027])