On December 22, 2025 Daiichi Sankyo and Astrazeneca reported the first patient has been dosed in the DESTINY-Endometrial02 phase 3 trial evaluating ENHERTU (trastuzumab deruxtecan) with or without radiotherapy compared to standard of care chemotherapy with or without radiotherapy as an adjuvant treatment (after surgery) in patients with HER2 expressing (IHC 3+/2+) endometrial cancer.
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DESTINY-Endometrial02 is being conducted in collaboration with The GOG Foundation, Inc. (GOG-F) and the European Network of Gynecological Oncological Trial Groups (ENGOT), with the French cooperative group (GINECO) as the lead ENGOT group.
ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).
While surgery is the recommended initial treatment for endometrial cancer, further treatment in the adjuvant setting is determined by the stage of disease and risk of recurrence.1,2 Following current standard of care adjuvant treatment, approximately 39% to 56% of patients with high-risk characteristics will experience disease recurrence or death within 18 months of diagnosis.3 HER2 expression (IHC 3+/2+) is present in approximately 18% to 56% of endometrial cancers and is associated with aggressive disease.4,5,6,7,8 There currently are no HER2 directed medicines approved in the adjuvant setting for HER2 expressing endometrial cancer.9,10
"Following the positive results of DESTINY-PanTumor02, which included a cohort of patients with metastatic endometrial cancer, we are now evaluating the use of ENHERTU in earlier lines of treatment for this disease," said Abderrahmane Laadem, MD, Head, Late-Stage Oncology Clinical Development, Daiichi Sankyo. "We recently initiated DESTINY-Endometrial01 to evaluate ENHERTU as a first-line treatment in patients with HER2 expressing primary advanced or recurrent endometrial cancer and are now initiating DESTINY-Endometrial02, the first trial to investigate a HER2 directed therapy in the adjuvant setting for patients with HER2 expressing endometrial cancer, to explore if ENHERTU can replace current standard of care chemotherapy and improve the long term outcome in this setting."
About DESTINY-Endometrial02
DESTINY-Endometrial02 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) with or without radiotherapy versus standard of care chemotherapy with or without radiotherapy as an adjuvant therapy in patients with treatment naïve HER2 expressing (IHC 3+/2+) endometrial cancer. Patients will be randomized 1:1 to receive either ENHERTU monotherapy or standard of care chemotherapy (carboplatin and paclitaxel). Both treatment arms may also receive radiotherapy.
The primary endpoint is disease-free survival (DFS) as assessed by blinded independent central review (BICR) or locally assessed histopathologic confirmation of disease recurrence. The key secondary endpoint is overall survival. Additional secondary endpoints include DFS as assessed by investigator; distant metastatic, local and regional recurrence as assessed by BICR or locally assessed histopathologic confirmation of disease recurrence; pharmacokinetics and safety.
DESTINY-Endometrial02 will enroll approximately 710 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.
About Endometrial Cancer
Endometrial cancer is the second most common gynecologic cancer and the sixth most common cancer among women worldwide.11 Approximately 420,000 endometrial cancer cases were diagnosed in 2022, with more than 97,000 deaths globally.12 Incidence and mortality rates of endometrial cancer are expected to increase by approximately 61% and 87% respectively by 2050.13
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors.14 HER2 expression (IHC 3+/ 2+) is present in approximately 18% to 56% of endometrial cancers and is associated with markers of aggressive disease.4,5,6,7,8
Surgery is the recommended initial treatment for all stages of endometrial cancer, while adjuvant therapy recommendations are determined by the stage of disease and risk of recurrence.1,2 Endometrial cancer has a five-year overall survival rate of 81.1%; however, following current standard of care adjuvant treatment, approximately 39% to 56% of patients with high-risk characteristics will experience disease recurrence or death within 18 months of diagnosis.3,15,16,17,18 Current adjuvant treatment options for patients with high-risk endometrial cancer are external beam radiation therapy (EBRT) with concurrent chemotherapy, sequential chemotherapy and radiotherapy or chemotherapy alone.1 There currently are no HER2 directed medicines approved in the adjuvant setting for HER2 expressing endometrial cancer.9,10
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) in combination with pertuzumab is approved in the U.S. as a first-line treatment for adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved test, based on the results from the DESTINY-Breast09 trial.
ENHERTU (5.4 mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+ or 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 55 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, DEC 22, 2025, View Source [SID1234661602])