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

A 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)

PHASE3 · Daiichi Sankyo · NCT07022483

This trial tests trastuzumab deruxtecan versus standard chemotherapy after surgery for adults with newly diagnosed HER2-expressing (IHC 3+/2+) endometrial cancer.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment710 (estimated)
Ages18 Years and up
SexFemale
SponsorDaiichi Sankyo (industry)
Drugs / interventionstrastuzumab, chemotherapy
Locations40 sites (Miami Beach, Florida and 39 other locations)
Trial IDNCT07022483 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18 years) with newly diagnosed FIGO 2023 Stage IIC or III epithelial endometrial carcinoma, centrally confirmed HER2 IHC 3+ or 2+, who are treatment-naïve post-surgery and eligible for adjuvant therapy.

Not a fit: Patients without HER2 expression (IHC 0–1+), those with sarcomas (except carcinosarcoma where allowed), or those who have received prior systemic anticancer therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could prolong disease-free survival and reduce recurrence risk for patients with HER2-expressing endometrial cancer.

How similar studies have performed: T-DXd has shown strong activity in HER2-positive breast and gastric cancers and early-phase signals in some HER2-expressing endometrial tumors, but adjuvant use in this population is a novel question being tested in this phase 3 trial.

Eligibility criteria

Show full inclusion / 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.

Where this trial is running

Miami Beach, Florida and 39 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Endometrial Cancer, endometrial cancer, cancer, T-DXd, HER2

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.