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
Launched by ASTRAZENECA · May 15, 2025
Trial Information
Current as of July 23, 2025
Recruiting
Keywords
ClinConnect Summary
The DESTINY-Endometrial01 trial is a research study looking at new treatment options for women with a specific type of advanced or recurrent endometrial cancer, which is a cancer of the uterus. This trial is testing two combinations of drugs: one that includes trastuzumab deruxtecan and rilvegostomig, and another with trastuzumab deruxtecan and pembrolizumab. These treatments are being compared to standard chemotherapy combined with pembrolizumab to see which works better at slowing down or stopping the cancer from getting worse.
To participate in this trial, women must be at least 18 years old and have been diagnosed with a type of endometrial cancer that shows certain markers (HER2 IHC 3+/2+) and is classified as mismatch repair proficient (pMMR). They should have either advanced stage cancer (Stage III or IV) or cancer that has come back after treatment. Participants will be closely monitored throughout the study to see how well the treatments work and if they are safe. This trial is currently recruiting, so eligible women can join if they meet the specific criteria outlined.
Gender
FEMALE
Eligibility 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.
About Astrazeneca
AstraZeneca is a global biopharmaceutical company dedicated to the discovery, development, and commercialization of innovative medicines across various therapeutic areas, including oncology, cardiovascular, respiratory, and autoimmune diseases. With a strong commitment to scientific research and patient-centric solutions, AstraZeneca leverages cutting-edge technology and a robust pipeline to address unmet medical needs. The company collaborates with healthcare professionals, academic institutions, and other organizations to advance clinical trials and deliver transformative therapies, aiming to improve health outcomes and enhance the quality of life for patients worldwide.
Contacts
Jennifer Cobb
Immunology at National Institute of Allergy and Infectious Diseases (NIAID)
Locations
Rochester, Minnesota, United States
Charlottesville, Virginia, United States
Skokie, Illinois, United States
Tampa, Florida, United States
Saint Louis, Missouri, United States
Gent, , Belgium
Liège, , Belgium
Białystok, , Poland
Augusta, Georgia, United States
Little Rock, Arkansas, United States
Cincinnati, Ohio, United States
Dresden, , Germany
New York, New York, United States
Zaragoza, , Spain
Manchester, , United Kingdom
Charlotte, North Carolina, United States
Leuven, , Belgium
Edmonton, Alberta, Canada
Winnipeg, Manitoba, Canada
London, Ontario, Canada
Toronto, Ontario, Canada
Napoli, , Italy
Roma, , Italy
Nijmegen, , Netherlands
Zurich, , Switzerland
Evanston, Illinois, United States
Milano, , Italy
Goiânia, , Brazil
Nice, , France
Paris, , France
Miami Beach, Florida, United States
Innsbruck, , Austria
Linz, , Austria
Vienna, , Austria
Helsinki, , Finland
Tampere, , Finland
Bordeaux, , France
Toulouse, , France
Rotterdam, , Netherlands
Madrid, , Spain
Baltimore, Maryland, United States
Worcester, Massachusetts, United States
Philadelphia, Pennsylvania, United States
Debrecen, , Hungary
Gdańsk, , Poland
La Jolla, California, United States
Sylmar, California, United States
Saint Petersburg, Florida, United States
Detroit, Michigan, United States
Minneapolis, Minnesota, United States
Hackensack, New Jersey, United States
Winston Salem, North Carolina, United States
Hershey, Pennsylvania, United States
Pittsburgh, Pennsylvania, United States
Montreal, Quebec, Canada
Herlev, , Denmark
Odense, , Denmark
Berlin, , Germany
Hamburg, , Germany
Uppsala, , Sweden
Leeds, , United Kingdom
Ann Arbor, Michigan, United States
Eugene, Oregon, United States
Boston, Massachusetts, United States
Marburg, , Germany
Münster, , Germany
Firenze, , Italy
San Sebastian, , Spain
Cambridge, , United Kingdom
Northwood, , United Kingdom
Shreveport, Louisiana, United States
East Melbourne, , Australia
Szczecin, , Poland
Lund, , Sweden
Leiden, , Netherlands
Taichung, , Taiwan
Tainan, , Taiwan
Providence, Rhode Island, United States
West Palm Beach, Florida, United States
South Brisbane, , Australia
Wein, , Austria
Essen, , Germany
Poznan, , Poland
Leipzig, , Germany
Siedlce, , Poland
Tucson, Arizona, United States
Sioux Falls, South Dakota, United States
Irving, Texas, United States
Seattle, Washington, United States
Beijing, , China
Chongqing, , China
Kaohsiung, , Taiwan
Bruxelles, , Belgium
Honolulu, Hawaii, United States
Halifax, Nova Scotia, Canada
Budapest, , Hungary
Tianjin, , China
Linköping, , Sweden
Las Vegas, Nevada, United States
Shinjuku Ku, , Japan
Niles, Illinois, United States
Abington, Pennsylvania, United States
Suwon Si, , Korea, Republic Of
Turku, , Finland
Milan, , Italy
Matsuyama Shi, , Japan
Morioka Shi, , Japan
Niigata Shi, , Japan
Jackson, Mississippi, United States
Nanning, , China
Wuhan, , China
Xian, , China
Changhua, , Taiwan
Rio De Janeiro, , Brazil
København ø, , Denmark
Koto Ku, , Japan
Mannheim, , Germany
Tokyo, , Japan
Sunto Gun, , Japan
Poitiers, , France
Taipei, , Taiwan
Stavanger, , Norway
Kassel, , Germany
El Palmar, , Spain
Montpellier, , France
Austin, Texas, United States
Palo Alto, California, United States
Changchun, , China
Chengdu, , China
Kunming, , China
Sendai Shi, , Japan
Madison, Wisconsin, United States
Guangzhou, , China
Shantou, , China
Seoul, , Korea, Republic Of
Oulu, , Finland
London, , United Kingdom
Monza, , Italy
Zürich, , Switzerland
Clermont Ferrand, , France
Nanchang, , China
Changsha, , China
Taiyuan, , China
Catania, , Italy
Sao Paulo, , Brazil
Saarbrücken, , Germany
Nedlands, , Australia
Kashiwa, , Japan
Kobe Shi, , Japan
Fuzhou, , China
Jinan, , China
Shanghai, , China
Albuquerque, New Mexico, United States
Saint Herblain, , France
Hangzhou, , China
Urumqi, , China
Sapporo Shi, , Japan
Osaka Shi, , Japan
L'hospitalet De Llobregat, , Spain
Porto Alegre, , Brazil
Isehara Shi, , Japan
Kurume Shi, , Japan
Anderlecht, , Belgium
Chemnitz, , Germany
Hidaka Shi, , Japan
Ota Shi, , Japan
Goyang Si, , Korea, Republic Of
łódź, , Poland
Palma De Mallorca, , Spain
Akashi Shi, , Japan
Blacktown, , Australia
Lanzhou, , China
Harbin, , China
New Taipei, , Taiwan
Hefei, , China
Aalborg, , Denmark
Cordoba, , Spain
Rome, , Italy
Xuzhou, , China
Salvador, , Brazil
Jining, , China
La Coruna, , Spain
Torino, , Italy
Frauenfeld, , Switzerland
Tulsa, Oklahoma, United States
Londrina, , Brazil
Kashiwa Shi, , Japan
Teresina, , Brazil
Nakagami Gun, , Japan
Fort Myers, Florida, United States
A Coruña, , Spain
Amsterdam, , Netherlands
Plerin, , France
Bath, , United Kingdom
Conroe, Texas, United States
Shenyang, , China
Turin, , Italy
Columbia, Maryland, United States
Liestal, , Switzerland
Fredericksburg, Texas, United States
Stockholm, , Sweden
Québec, Quebec, Canada
Montréal, Quebec, Canada
Yibin, , China
Saint Johnsbury, Vermont, United States
Dessau Roßlau, , Germany
Belo Horizonte, , Brazil
São Paulo, , Brazil
Reggio Emilia, , Italy
Valencia, , Spain
Barretos, , Brazil
Charleroi, , Belgium
Calgary, Alberta, Canada
Oslo, , Norway
Cincinnati, Ohio, United States
Haikou City, , China
Patients applied
Timeline
First submit
Trial launched
Trial updated
Estimated completion
Not reported