RECRUITING

DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC 3+/2+), Mismatch Repair Proficient (pMMR) Endometrial Cancer

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

DESTINY-Endometrial01 will investigate the efficacy of first-line T-DXd + rilvegostomig (Arm A) and/or T-DXd+ pembrolizumab (Arm B) when compared to chemotherapy (carboplatin + paclitaxel) + pembrolizumab (Arm C), by assessment of progression free survival (PFS), as assessed by BICR, in participants with HER2-expressing (IHC 3+/2+), pMMR, primary advanced (Stage III/IV) or recurrent EC.

Official Title

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

Quick Facts

Study Start:2025-03-27
Study Completion:2031-02-20
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06989112

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:FEMALE
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Participants must be ≥ 18 years of age at the time of screening. Other age restrictions may apply as per local regulations.
  2. * Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies are allowed except for sarcomas (carcinosarcomas are allowed).
  3. * 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:
  4. * Primary Stage III (per FIGO 2023) disease with measurable disease at baseline per RECIST 1.1 based on the investigator's assessment.
  5. * Primary Stage IV disease (per FIGO 2023) regardless of presence of measurable disease at baseline.
  6. * First recurrent disease regardless of presence of measurable disease at baseline.
  7. * Endometrial cancer with HER2 IHC expression of 3+ or 2+ as assessed by prospective central testing.
  8. * Endometrial cancer that is determined pMMR by prospective central IHC testing.
  9. * 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.
  10. * Prior therapy:
  11. * 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.
  12. * 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.
  13. * 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.
  14. * Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
  15. * Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before randomization.
  16. * Adequate organ and bone marrow function within 14 days before randomization.
  17. * Key
  1. * History of organ transplant
  2. * 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.
  3. * Spinal cord compression or clinically active central nervous system metastases
  4. * 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
  5. * 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.
  6. * Lung criteria:
  7. * 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.).
  8. * Any autoimmune, connective tissue or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at the time of screening.
  9. * Prior pneumonectomy (complete).
  10. * Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
  11. * Active primary immunodeficiency/ active infectious disease(s) including:
  12. * Tuberculosis (TB)
  13. * HIV infection that is not well controlled.
  14. * 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.
  15. * 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.

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center
CONTACT
1-877-240-9479
information.center@astrazeneca.com

Study Locations (Sites)

Research Site
Tucson, Arizona, 85704
United States
Research Site
Little Rock, Arkansas, 72205
United States
Research Site
La Jolla, California, 92037
United States
Research Site
Palo Alto, California, 94304
United States
Research Site
Sylmar, California, 91342
United States
Research Site
Fort Myers, Florida, 33908
United States
Research Site
Miami Beach, Florida, 33140
United States
Research Site
Saint Petersburg, Florida, 33705
United States
Research Site
Tampa, Florida, 33612
United States
Research Site
West Palm Beach, Florida, 33401
United States
Research Site
Augusta, Georgia, 30912
United States
Research Site
Honolulu, Hawaii, 96813
United States
Research Site
Niles, Illinois, 60714
United States
Research Site
Skokie, Illinois, 60077
United States
Research Site
Shreveport, Louisiana, 71103
United States
Research Site
Columbia, Maryland, 21201-1544
United States
Research Site
Boston, Massachusetts, 02111
United States
Research Site
Worcester, Massachusetts, 01655
United States
Research Site
Ann Arbor, Michigan, 48109
United States
Research Site
Detroit, Michigan, 48201
United States
Research Site
Minneapolis, Minnesota, 55455
United States
Research Site
Jackson, Mississippi, 39213
United States
Research Site
Jackson, Mississippi, 39216
United States
Research Site
Saint Louis, Missouri, 63141
United States
Research Site
Las Vegas, Nevada, 89169
United States
Research Site
Hackensack, New Jersey, 07601
United States
Research Site
Albuquerque, New Mexico, 87109
United States
Research Site
New York, New York, 10016
United States
Research Site
New York, New York, 10065
United States
Research Site
New York, New York, 10075
United States
Research Site
Winston-Salem, North Carolina, 27103
United States
Research Site
Cincinnati, Ohio, 45202
United States
Research Site
Tulsa, Oklahoma, 74134
United States
Research Site
Eugene, Oregon, 97401
United States
Research Site
Abington, Pennsylvania, 19001
United States
Research Site
Hershey, Pennsylvania, 17033
United States
Research Site
Pittsburgh, Pennsylvania, 15224
United States
Research Site
Providence, Rhode Island, 02905
United States
Research Site
Sioux Falls, South Dakota, 57105
United States
Research Site
Conroe, Texas, 77384
United States
Research Site
Fredericksburg, Texas, 78624
United States
Research Site
Irving, Texas, 75063
United States
Research Site
Saint Johnsbury, Vermont, 05819
United States
Research Site
Charlottesville, Virginia, 22908
United States
Research Site
Seattle, Washington, 98133
United States
Research Site
Madison, Wisconsin, 53705
United States

Collaborators and Investigators

Sponsor: AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-03-27
Study Completion Date2031-02-20

Study Record Updates

Study Start Date2025-03-27
Study Completion Date2031-02-20

Terms related to this study

Keywords Provided by Researchers

  • Endometrial Cancer
  • Uterine Cancer
  • Endometrial Carcinoma
  • Human epidermal growth factor receptor 2 (HER2)
  • PMMR
  • Trastuzumab deruxtecan
  • T-DXd
  • DS-8201a
  • Anti-HER2-Antibody Drug Conjugate(ADC)
  • DESTINY-Endometrial01
  • Programmed Cell Death-1 (PD1, PD-1)
  • Immune checkpoint inhibitor
  • TIGIT
  • Pembrolizumab
  • Carboplatin
  • Paclitaxel
  • Rilvegostomig

Additional Relevant MeSH Terms

  • Endometrial Cancer