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New treatment options for advanced endometrial cancer

DESTINY-Endometrial01: An Open-Label, Sponsor-Blinded, Randomized, Controlled, Multicenter, Phase III Study of Trastuzumab Deruxtecan (T-DXd) Plus Rilvegostomig or Pembrolizumab vs Chemotherapy Plus Pembrolizumab as First-Line Therapy of HER2-Expressing (IHC 3+/2+), Mismatch Repair Proficient (pMMR), Primary Advanced or Recurrent Endometrial Cancer

Phase 3 Interventional AstraZeneca · NCT06989112

This study is testing a new combination of treatments for advanced endometrial cancer to see if it can help patients live longer without their cancer getting worse compared to standard chemotherapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years and up
SexFemale
SponsorAstraZeneca Industry-sponsored
Drugs / interventionstrastuzumab, chemotherapy, radiation, pembrolizumab
Locations250 sites (Tucson, Arizona and 249 other locations)
Trial IDNCT06989112 on ClinicalTrials.gov

What this trial studies

DESTINY-Endometrial01 is a Phase III clinical trial that evaluates the effectiveness of trastuzumab deruxtecan combined with either rilvegostomig or pembrolizumab as first-line treatments for patients with HER2-expressing endometrial cancer. The study compares these combinations against standard chemotherapy with carboplatin and paclitaxel plus pembrolizumab. The primary outcome measure is progression-free survival, assessed by independent central review in participants with advanced or recurrent disease. This trial aims to provide new therapeutic options for patients with specific cancer characteristics.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with HER2-expressing, mismatch repair proficient endometrial cancer at advanced stages or with first recurrence.

Not a fit: Patients with endometrial cancer that does not express HER2 or those with sarcomas may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer more effective treatment options for patients with advanced endometrial cancer, potentially improving survival rates.

How similar studies have performed: Other studies have shown promising results with similar HER2-targeted therapies in various cancers, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
* Key Inclusion Criteria:

  * Participants must be ≥ 18 years of age at the time of screening. Other age restrictions may apply as per local regulations.
  * Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies are allowed except for sarcomas (carcinosarcomas are allowed).
  * Following surgery or diagnostic biopsy, participant must have primary advanced disease (Stage III/IV) or first recurrent endometrial cancer and meet at least one of the following criteria:

    * Primary Stage III (per FIGO 2023) disease with measurable disease at baseline per RECIST 1.1 based on the investigator's assessment.
    * Primary Stage IV disease (per FIGO 2023) regardless of presence of measurable disease at baseline.
    * First recurrent disease regardless of presence of measurable disease at baseline.
  * Endometrial cancer with HER2 IHC expression of 3+ or 2+ as assessed by prospective central testing.
  * Endometrial cancer that is determined pMMR by prospective central IHC testing.
  * Provision of adequate FFPE tumor tissue sample of a tumor lesion that was not previously irradiated for central HER2, MMR, and PD-L1 IHC testing and valid central test results for randomization/ stratification.
  * Prior therapy:

    * Naïve to first-line systemic anticancer therapy. Participants may have received one prior line of adjuvant/neoadjuvant chemotherapy with curative intent (chemotherapy or chemoradiation) if disease recurrence or progression occurred ≥ 6 months after last dose of chemotherapy. Prior trastuzumab in the adjuvant/neoadjuvant setting is allowed.
    * No prior exposure to ADCs or immune checkpoint inhibitors including (but not limited to) anti-PD-1/PD-L1/PD-L2 and anti-CTLA-4 antibodies and therapeutic anticancer vaccines.
    * Participants may have received prior radiation therapy for the treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy. Adequate treatment washout period is required.
  * Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
  * Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before randomization.
  * Adequate organ and bone marrow function within 14 days before randomization.
* Key Exclusion Criteria:

  * History of organ transplant
  * Uncontrolled intercurrent illness, including, but not limited to ongoing or active known infection, serious chronic gastrointestinal conditions associated with diarrhea and active non-infectious skin disease requiring systemic treatment.
  * Spinal cord compression or clinically active central nervous system metastases
  * Participants with a medical history of myocardial infarction (MI) within 6 months before randomization, or symptomatic congestive heart failure (CHF) (NYHA Class II to IV), clinically significant arrhythmia, or cardiomyopathy of any etiology. Participants with troponin levels above ULN at screening (as defined by the manufacturer), should have a cardiologic consultation before enrollment to rule out MI
  * History of (non-infectious) ILD/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
  * Lung criteria:

    * Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.).
    * Any autoimmune, connective tissue or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at the time of screening.
    * Prior pneumonectomy (complete).
  * Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
  * Active primary immunodeficiency/ active infectious disease(s) including:

    * Tuberculosis (TB)
    * HIV infection that is not well controlled.
    * Chronic or active hepatitis B, chronic or active hepatitis C; however, participants who have chronic hepatitis B and are receiving suppressive antiviral therapy are allowed to be enrolled if alanine aminotransferase (ALT) is normal and viral load is controlled.
  * Any concurrent anticancer treatment without an adequate washout period prior to the first dose of study intervention. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., HRT) is allowed.

Where this trial is running

Tucson, Arizona and 249 other locations

+200 more sites — see ClinicalTrials.gov for the full list.

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 → Find more trials like this →
Conditions Endometrial CancerUterine CancerEndometrial CarcinomaHuman epidermal growth factor receptor 2PMMRTrastuzumab deruxtecanT-DXdDS-8201a
Last reviewed 2026-06-13 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.