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

NCT07022483 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: DS8201-854
• Study Type: interventional
• Target: 710
• Locations: 5 countries
• Sites: 40

Brief Summary

This study is designed to assess efficacy and safety of T-DXd adjuvant therapy, with or without radiotherapy, post-surgery in anticancer treatment naïve (including neoadjuvant therapy) endometrial cancer with various HER2 expression levels.

Conditions

Endometrial Cancer

Keywords

endometrial cancer; cancer; T-DXd; HER2

Outcome Measures

Primary Outcomes (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.

  From randomization to the first documented local regional recurrence, distant metastasis, or death due to any cause, whichever occurs first, up to approximately 51 months

Secondary Outcomes (1)

• Overall Survival

  From randomization to the date of death due to any cause, up to approximately 63 months

Study Arms (2)

Arm A: T-DXd

EXPERIMENTAL

Participants will receive T-DXd 5.4 mg/kg intravenously (IV) once every 3 weeks (Q3W) with or without \[optional\] radiotherapy

Drug: Trastuzumab Deruxtecan

Arm B: Standard of Care Chemotherapy

ACTIVE COMPARATOR

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

Interventions

Trastuzumab Deruxtecan DRUG

T-DXd will be administered at a dose of 5.4 mg/kg IV Q3W.

Also known as: T-DXd, ENHERTU®

Arm A: T-DXd

Chemotherapy DRUG

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.

Arm B: Standard of Care Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• AstraZeneca: collaborator

Study Sites (40)

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

RECRUITING

Trials365 LLC

Shreveport, Louisiana, 71103, United States

RECRUITING

Avera Medical Group Gynecologic Oncology Sioux Falls

Sioux Falls, South Dakota, 57105, United States

RECRUITING

Beijing Cancer Hospital

Beijing, China

RECRUITING

The First Hospital of Jilin University

Changchun, China

RECRUITING

West China Second University Hospital, Sichuan University

Chengdu, China

RECRUITING

Obstetrics and Gynecology Hospital Affiliated to Zhejiang University School of Medicine

Hangzhou, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, China

RECRUITING

Cancer Hospital of Shandong First Medical University

Jinan, China

RECRUITING

Linyi Cancer Hospital

Linyi, China

RECRUITING

Jiangxi Maternal and Child Health Hospital

Nanchang, China

RECRUITING

Guangxi Medical University Affiliated Tumor Hospital

Nanning, China

RECRUITING

Shanghai First Maternity and Infant HospitalShanghai First Maternity and Infant Hospital

Shanghai, China

RECRUITING

Shanghai Tenth People's Hospital

Shanghai, China

RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, China

RECRUITING

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, China

RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, China

RECRUITING

Yantai Yuhuangding Hospital

Yantai, China

RECRUITING

Hyogo Cancer Center

Akashi-shi, Japan

RECRUITING

NHO Kyushu Cancer Center

Fukuoka, Japan

RECRUITING

Fukushima Medical University Hospital

Fukushima, Japan

RECRUITING

Saitama Medical University International Medical Center

Hidaka-shi, Japan

RECRUITING

Cancer Institute Hospital of JFCR

Kōtoku, Japan

RECRUITING

Kurume University Hospital

Kurume-shi, Japan

RECRUITING

Niigata Cancer Center Hospital

Niigata, Japan

RECRUITING

Okayama University Hospital

Okayama, Japan

RECRUITING

Gunma Prefectural Cancer Center

Ota-shi, Japan

RECRUITING

NHO Hokkaido Cancer Center

Sapporo, Japan

RECRUITING

Tohoku University Hospital

Sendai, Japan

RECRUITING

Keio University Hospital

Shinjuku-ku, Japan

RECRUITING

Mie University Hospital

Tsu, Japan

RECRUITING

Yamagata University Hospital

Yamagata, Japan

RECRUITING

Keimyung University Dongsan Hospital

Daegu, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Taichung Veterans General Hospital

Taichung, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, Taiwan

RECRUITING

MeSH Terms

Conditions

Endometrial Neoplasms; Neoplasms

Interventions

trastuzumab deruxtecan; Drug Therapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Contact for Trial Information

CONTACT

908-992-6400; CTRinfo_us@daiichisankyo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 15, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): March 23, 2032
• Study Completion (Estimated): March 23, 2032
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

TW (4); US (3); JP (14); KR (3); CN (16)