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Search / Trial NCT06989112

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

Endometrial Cancer Uterine Cancer Endometrial Carcinoma Human Epidermal Growth Factor Receptor 2 (Her2) Pmmr Trastuzumab Deruxtecan T D Xd 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

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.

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

0 patients applied

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported