Study of Trastuzumab Deruxtecan Versus Standard of Care Chemotherapy for HER2-Expressing (IHC 3+/2+) Endometrial Cancer

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified April 2026 by Daiichi Sankyo
Sponsor
Daiichi Sankyo
Information Provided by (Responsible Party)
Daiichi Sankyo
Clinicaltrials.gov Identifier
NCT07022483
Other Study ID Numbers:
DS8201-854
First Submitted
June 5, 2025
First Posted
June 14, 2025
Last Update Posted
May 27, 2026
Last Verified
April 2026

ClinicalTrials.gov processed this data on May 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

This is a global, multicenter, open-label, phase 3 study to evaluate the efficacy and safety of T-DXd versus SoC chemotherapy with or without radiotherapy as adjuvant treatment in participants with HER2-expressing (IHC 3+/2+) endometrial cancer. Participants will be randomized 1:1 to either T-DXd or SoC chemotherapy. The primary objective will assess disease-free survival as assessed radiographically by BICR or by histopathologic confirmation of disease recurrence per local assessment.

T-DXd (Enhertu®) is a HER2 directed ADC composed of a humanized anti-HER2 IgG1 mAb with the same amino acid sequence as trastuzumab, which includes a plasma-stable, selectively cleavable linker and potent topoisomerase I inhibitor payload (a derivative of exatecan) that leverages the clinically validated DXd ADC technology.

Condition or DiseaseIntervention/Treatment
Endometrial Cancer
Drug: Trastuzumab DeruxtecanDrug: Chemotherapy

Study Design

Study TypeInterventional
Actual Enrollment710 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Phase 3, Multicenter, Randomized, Open-label Trial of Trastuzumab Deruxtecan Versus Standard of Care Chemotherapy With or Without Radiotherapy as Adjuvant Treatment for HER2-Expressing (IHC 3+/2+) Endometrial Cancer (DESTINY-Endometrial02/ GOG-3122/ ENGOT-en30/GINECO)
Study Start DateSeptember 29, 2025
Actual Primary Completion Date5yrs 9mos from now
Actual Study Completion Date5yrs 9mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Arm A: T-DXd
Participants will receive T-DXd 5.4 mg/kg intravenously (IV) once every 3 weeks (Q3W) with or without \[optional\] radiotherapy
Drug: Trastuzumab Deruxtecan
T-DXd will be administered at a dose of 5.4 mg/kg IV Q3W.
Arm B: Standard of Care Chemotherapy
Participants will receive carboplatin AUC 5 or 6 and paclitaxel 175 mg/m2 Q3W, or AUC 5 or 6 and paclitaxel 175 mg/m2 Q3W with or without \[optional\] radiotherapy or chemoradiotherapy (EBRT plus cisplatin \[as radiosensitizer\] 50 mg/m2
Drug: Chemotherapy
Carboplatin AUC 5 or 6 and paclitaxel will be administered at a dose of 175 mg/m2 Q3W, or carboplatin AUC 5 or 6 and paclitaxel 175 mg/m2 Q3W followed by chemoradiotherapy.

Outcome Measures

Primary Outcome Measures
  1. Disease-Free Survival as Assessed by Blinded Independent Central Review or by Histopathologic Confirmation of Disease Recurrence per Local Assessment
    Disease-Free Survival will be assessed radiographically by BICR or by histopathologic confirmation of disease recurrence per local assessment.
Secondary Outcome Measures
  1. Overall Survival
    Overall Survival is defined as the time interval from the date of randomization to the date of death due to any cause.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyFemale
Accepts Healthy VolunteersNo
Inclusion Criteria
Key Inclusion Criteria
Adults ≥18 years at the time the ICF is signed (Please follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old)
Has histologically confirmed diagnosis of epithelial endometrial carcinoma. All histology's are allowed except for sarcomas (carcinosarcomas are allowed).
Is newly diagnosed FIGO 2023 Stage IIC (including Stage IICmp53abn) or Stage III Note: FIGO 2023 Stage IIC includes disease with aggressive histological types (aggressive histological types are composed of high-grade EECs (grade 3), serous, clear cell, undifferentiated, mixed, mesonephric-like, gastrointestinal mucinous type carcinomas, and carcinosarcomas) with any myometrial involvement. FIGO 2023 Stage III includes disease with local and/or regional spread of the tumor of any histological subtype.
Has HER2-expression (IHC 3+/2+) per 2016 ASCO-CAP gastric cancer IHC scoring guidelines as confirmed by central laboratory testing.
Has adequate archived tumor tissue sample (sample from surgery is strongly recommended) available for assessment of HER2 status by central laboratory. Key
Exclusion Criteria
Key Inclusion Criteria
Adults ≥18 years at the time the ICF is signed (Please follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old)
Has histologically confirmed diagnosis of epithelial endometrial carcinoma. All histology's are allowed except for sarcomas (carcinosarcomas are allowed).
Is newly diagnosed FIGO 2023 Stage IIC (including Stage IICmp53abn) or Stage III Note: FIGO 2023 Stage IIC includes disease with aggressive histological types (aggressive histological types are composed of high-grade EECs (grade 3), serous, clear cell, undifferentiated, mixed, mesonephric-like, gastrointestinal mucinous type carcinomas, and carcinosarcomas) with any myometrial involvement. FIGO 2023 Stage III includes disease with local and/or regional spread of the tumor of any histological subtype.
Has HER2-expression (IHC 3+/2+) per 2016 ASCO-CAP gastric cancer IHC scoring guidelines as confirmed by central laboratory testing.
Has adequate archived tumor tissue sample (sample from surgery is strongly recommended) available for assessment of HER2 status by central laboratory. Key Exclusion Criteria
Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas are also not allowed.
Has recurrent or FIGO 2023 Stage IV
Has measurable residual tumor after surgery as determined by BICR assessment.
Is known to have a POLE mutation from an approved and/or validated local test, according to local regulations, if available
Has a medical history of MI within 6 months before randomization/enrollment, symptomatic CHF (NYHA Class II to IV). Participants with troponin levels above ULN at SCR (as defined by the manufacturer), and without any MI related symptoms should have a cardiologic consultation during SCR Period to rule out MI.
Has a QTcF prolongation to \> 480 msec based on average of the SCR triplicate12-lead ECG. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the trial enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.) and any autoimmune, connective tissue, or inflammatory disorder with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
Has a history of (noninfectious) ILD/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at SCR.

Contacts and Locations

Sponsors and CollaboratorsDaiichi Sankyo
Locations
Broward Health Medical Center | Fort Lauderdale Florida, United States, 33316Miami Cancer Institute | Miami Florida, United States, 33176Mount Sinai Medical Center | Miami Beach Florida, United States, 33140Trials365 LLC | Shreveport Louisiana, United States, 71103FirstHealth of the Carolinas, Inc. | Pinehurst North Carolina, United States, 28374University of Cincinnati Physicians Group, LLC | Cincinnati Ohio, United States, 45206Avera Medical Group Gynecologic Oncology Sioux Falls | Sioux Falls South Dakota, United States, 57105Texas Oncology San Antonio Medical Center | San Antonio Texas, United States, 78240Hospital Italiano de Buenos Aires | Ciudad Autonoma Buenos Aires , Argentina, C1199Sanatorio Allende Cerro | Córdoba , Argentina, X5021FPQCentro de Investigaciones Medicas Mar del Plata | Mar del Plata , Argentina, B7600Beijing Cancer Hospital | Beijing , China, The First Hospital of Jilin University | Changchun , China, West China Second University Hospital, Sichuan University | Chengdu , China, Obstetrics and Gynecology Hospital Affiliated to Zhejiang University School of Medicine | Hangzhou , China, Zhejiang Cancer Hospital | Hangzhou , China, Cancer Hospital of Shandong First Medical University | Jinan , China, Linyi Cancer Hospital | Linyi , China, Jiangxi Maternal and Child Health Hospital | Nanchang , China, Guangxi Medical University Affiliated Tumor Hospital | Nanning , China, Shanghai First Maternity and Infant HospitalShanghai First Maternity and Infant Hospital | Shanghai , China, Shanghai Tenth People's Hospital | Shanghai , China, Tianjin Medical University Cancer Institute & Hospital | Tianjin , China, The First Affiliated Hospital of Wenzhou Medical University | Wenzhou , China, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology | Wuhan , China, Union Hospital Tongji Medical College Huazhong University of Science and Technology | Wuhan , China, Yantai Yuhuangding Hospital | Yantai , China, Centre Francois Baclesse | Caen , France, 14076Institut Claudius Regaud | Toulouse , France, 31059Klinikum Lippe-Detmold | Detmold , Germany, 32756Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS | Bologna , Italy, 40138Azienda Ospedaliera Universitaria Careggi | Florence , Italy, 50134IEO Istituto Europeo di Oncologia | Milan , Italy, 20141Ospedale Mauriziano Umberto I | Torino , Italy, 10128Hyogo Cancer Center | Akashi-shi , Japan, NHO Kyushu Cancer Center | Fukuoka , Japan, Fukushima Medical University Hospital | Fukushima , Japan, Saitama Medical University International Medical Center | Hidaka-shi , Japan, Cancer Institute Hospital of JFCR | Kōtoku , Japan, Kurume University Hospital | Kurume-shi , Japan, Niigata Cancer Center Hospital | Niigata , Japan, Okayama University Hospital | Okayama , Japan, Gunma Prefectural Cancer Center | Ota-shi , Japan, NHO Hokkaido Cancer Center | Sapporo , Japan, Tohoku University Hospital | Sendai , Japan, Keio University Hospital | Shinjuku-ku , Japan, Mie University Hospital | Tsu , Japan, Yamagata University Hospital | Yamagata , Japan, Hospital da Luz | Lisbon , Portugal, 1500-650Keimyung University Dongsan Hospital | Daegu , South Korea, Samsung Medical Center | Seoul , South Korea, Seoul National University Hospital | Seoul , South Korea, Complejo Hospitalario Universitario A Coruña | A Coruña , Spain, 15006Hospital Universitario Virgen de la Arrixaca | El Palmar , Spain, 30120Hospital Universitario Ramon y Cajal | Madrid , Spain, 28034Hospital Universitario 12 de Octubre | Madrid , Spain, 28041Hospital Universitari Son Espases | Palma de Mallorca , Spain, 07120Taichung Veterans General Hospital | Taichung , Taiwan, National Cheng Kung University Hospital | Tainan , Taiwan, National Taiwan University Hospital | Taipei , Taiwan, Taipei Veterans General Hospital | Taipei , Taiwan,