Trastuzumab deruxtecan versus standard chemotherapy for HER2-expressing (IHC 3+/2+) endometrial cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This global, multicenter, open-label phase 3 trial randomizes participants 1:1 to receive adjuvant trastuzumab deruxtecan (T-DXd) or standard-of-care chemotherapy with or without radiotherapy following surgery. Eligible patients are adults with newly diagnosed FIGO 2023 Stage IIC or Stage III epithelial endometrial carcinoma that centrally confirms HER2 expression by IHC 3+ or 2+. The primary endpoint is disease-free survival determined by blinded independent central radiographic review or by local histopathologic confirmation of recurrence. Safety and tolerability of T-DXd compared with standard chemotherapy are also measured during follow-up.

Why it matters

Who can join: the full rules

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+).
* Has adequate archived tumor tissue sample 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 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.

Where it's running

• Broward Health Medical Center
  Fort Lauderdale, Florida, United States Recruiting
• Miami Cancer Institute
  Miami, Florida, United States Recruiting
• Mount Sinai Medical Center
  Miami Beach, Florida, United States Recruiting
• AdventHealth
  Orlando, Florida, United States Recruiting
• Parkview Research Center
  Fort Wayne, Indiana, United States Recruiting
• Trials365 LLC
  Shreveport, Louisiana, United States Recruiting

+36 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Contact for Trial Information
• Email: CTRinfo_us@daiichisankyo.com
• Phone: 908-992-6400

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.