RECRUITING Phase 3 ClinicalTrials.gov

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

Sponsor: AstraZeneca • ClinicalTrials.gov ID: NCT06989112

Registry updated: 2026-10-13

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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.

Interventions

Trastuzumab deruxtecan (Drug)
Experimental therapy by intravenous infusion
Rilvegostomig (Drug)
Experimental therapy by intravenous infusion
Pembrolizumab (Drug)
Immunotherapy by intravenous infusion
Carboplatin (Drug)
Standard of Care (SoC) chemotherapy by intravenous infusion
Paclitaxel (Drug)
Standard of Care (SoC) chemotherapy by intravenous infusion
Docetaxel (Drug)
Standard of Care (SoC) chemotherapy by intravenous infusion

Eligibility criteria

Key Inclusion Criteria: * ≥ 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). * Participant must have primary advanced disease (Stage III/IV) or recurrent endometrial cancer and meet at least one of the following criteria: 1. Primary Stage III (per FIGO 2023) disease with measurable disease at baseline per RECIST 1.1 based on the investigator's assessment. 2. Primary Stage IV (per FIGO 2023) disease regardless of presence of measurable disease at baseline. 3. Recurrent disease regardless of presence of measurable disease at baseline. * Endometrial cancer with HER2 IHC expression of 3+ or 2+ by prospective central testing. * Endometrial cancer that is determined pMMR by prospective central testing. * Provision of an adequate FFPE tumor tissue sample for central HER2, MMR, and PD-L1 IHC testing. * Prior therapy: 1. No prior chemotherapy for the treatment of EC, except for one prior line of adjuvant/ neoadjuvant chemotherapy with curative intent (chemotherapy or chemoradiation) if completed ≥ 6 months prior to signature of the main ICF. Prior trastuzumab in the adjuvant/neoadjuvant setting is allowed. 2. No prior exposure to antibody-drug conjugates or immune checkpoint inhibitors 3. Participants may have received prior radiation therapy for the treatment of endometrial cancer. Adequate treatment washout period is required 4. Participants may have received prior hormonal therapy for the treatment of endometrial cancer. Adequate treatment washout period is required * ECOG 0-1. * Left ventricular ejection fraction ≥ 50% within 28 days before randomization. * Adequate organ and bone marrow function within 14 days before randomization. * The participant is not considered a candidate for curative therapy in the judgment of the investigator. Key Exclusion Criteria: * Any severe or uncontrolled systemic diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or would jeopardize compliance with the protocol. * Active or ongoing serious chronic gastrointestinal conditions associated with diarrhea, primary immunodeficiency, or non-infectious skin disease requiring systemic treatment. * Active or prior documented autoimmune or inflammatory disorders requiring chronic systemic treatment with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs. * 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: 1. 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, etc.). 2. Any autoimmune, connective tissue or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at the time of screening. 3. Prior pneumonectomy (complete). * History of myocardial infarction or unstable angina within 6 months before randomization, or symptomatic congestive heart failure (NYHA Class II to IV), clinically significant arrhythmia, uncontrolled hypertension, cardiomyopathy of any etiology or history of myocarditis. * History of organ transplant or allogeneic stem cell transplant. * Spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases may be included in the study. * Evidence of any of the following infections: 1. Active tuberculosis 2. HIV infection that is not well controlled. 3. Active hepatitis B or C infection.

Conditions

Endometrial Cancer

Locations

Research Site — Tucson, Arizona, United States
Research Site — Little Rock, Arkansas, United States
Research Site — Duarte, California, United States
Research Site — Irvine, California, United States
Research Site — La Jolla, California, United States
Research Site — Palo Alto, California, United States
Research Site — San Francisco, California, United States
Research Site — Sylmar, California, United States
Research Site — Fort Myers, Florida, United States
Research Site — Miami, Florida, United States
Research Site — Miami Beach, Florida, United States
Research Site — Orlando, Florida, United States
Research Site — St. Petersburg, Florida, United States
Research Site — Tampa, Florida, United States
Research Site — West Palm Beach, Florida, United States
Research Site — Augusta, Georgia, United States
Research Site — Honolulu, Hawaii, United States
Research Site — Arlington Heights, Illinois, United States
Research Site — Evanston, Illinois, United States
Research Site — Shreveport, Louisiana, United States
Research Site — Baltimore, Maryland, United States
Research Site — Silver Spring, Maryland, United States
Research Site — Boston, Massachusetts, United States
Research Site — Worcester, Massachusetts, United States
Research Site — Ann Arbor, Michigan, United States
Research Site — Detroit, Michigan, United States
Research Site — Marshall, Minnesota, United States
Research Site — Minneapolis, Minnesota, United States
Research Site — Rochester, Minnesota, United States
Research Site — Jackson, Mississippi, United States
Research Site — Springfield, Missouri, United States
Research Site — St Louis, Missouri, United States
Research Site — Las Vegas, Nevada, United States
Research Site — Lebanon, New Hampshire, United States
Research Site — Hackensack, New Jersey, United States
Research Site — Albuquerque, New Mexico, United States
Research Site — New York, New York, United States
Research Site — New York, New York, United States
Research Site — New York, New York, United States
Research Site — Charlotte, North Carolina, United States
Research Site — Charlotte, North Carolina, United States
Research Site — Winston-Salem, North Carolina, United States
Research Site — Winston-Salem, North Carolina, United States
Research Site — Cincinnati, Ohio, United States
Research Site — Columbus, Ohio, United States
Research Site — Oklahoma City, Oklahoma, United States
Research Site — Tulsa, Oklahoma, United States
Research Site — Eugene, Oregon, United States
Research Site — Abington, Pennsylvania, United States
Research Site — Hershey, Pennsylvania, United States
Research Site — Philadelphia, Pennsylvania, United States
Research Site — Pittsburgh, Pennsylvania, United States
Research Site — Providence, Rhode Island, United States
Research Site — Charleston, South Carolina, United States
Research Site — Sioux Falls, South Dakota, United States
Research Site — Austin, Texas, United States
Research Site — Fort Worth, Texas, United States
Research Site — Houston, Texas, United States
Research Site — San Antonio, Texas, United States
Research Site — Charlottesville, Virginia, United States
Research Site — Fairfax, Virginia, United States
Research Site — Seattle, Washington, United States
Research Site — Madison, Wisconsin, United States
Research Site — Blacktown, Australia
Research Site — East Melbourne, Australia
Research Site — Nedlands, Australia
Research Site — South Brisbane, Australia
Research Site — Innsbruck, Austria
Research Site — Linz, Austria
Research Site — Vienna, Austria
Research Site — Wein, Austria
Research Site — Anderlecht, Belgium
Research Site — Brussels, Belgium
Research Site — Charleroi, Belgium
Research Site — Ghent, Belgium
Research Site — Leuven, Belgium
Research Site — Liège, Belgium
Research Site — Barretos, Brazil
Research Site — Belo Horizonte, Brazil
Research Site — Goiânia, Brazil
Research Site — Londrina, Brazil
Research Site — Porto Alegre, Brazil
Research Site — Porto Alegre, Brazil
Research Site — Rio de Janeiro, Brazil
Research Site — Salvador, Brazil
Research Site — São Paulo, Brazil
Research Site — São Paulo, Brazil
Research Site — São Paulo, Brazil
Research Site — Teresina, Brazil
Research Site — Calgary, Alberta, Canada
Research Site — Edmonton, Alberta, Canada
Research Site — Winnipeg, Manitoba, Canada
Research Site — Halifax, Nova Scotia, Canada
Research Site — London, Ontario, Canada
Research Site — Toronto, Ontario, Canada
Research Site — Toronto, Ontario, Canada
Research Site — Montreal, Quebec, Canada
Research Site — Montreal, Quebec, Canada
Research Site — Montreal, Quebec, Canada
Research Site — Montreal, Quebec, Canada
Research Site — Québec, Quebec, Canada
Research Site — Beijing, China
Research Site — Changchun, China
Research Site — Changsha, China
Research Site — Chengdu, China
Research Site — Chengdu, China
Research Site — Chongqing, China
Research Site — Fuzhou, China
Research Site — Fuzhou, China
Research Site — Guangzhou, China
Research Site — Guangzhou, China
Research Site — Guangzhou, China
Research Site — Haikou, China
Research Site — Hangzhou, China
Research Site — Harbin, China
Research Site — Hefei, China
Research Site — Jinan, China
Research Site — Jinan, China
Research Site — Jining, China
Research Site — Kunming, China
Research Site — Lanzhou, China
Research Site — Nanchang, China
Research Site — Nanning, China
Research Site — Shanghai, China
Research Site — Shanghai, China
Research Site — Shantou, China
Research Site — Shenyang, China
Research Site — Shenyang, China
Research Site — Taiyuan, China
Research Site — Tianjin, China
Research Site — Ürümqi, China
Research Site — Wuhan, China
Research Site — Wuhan, China
Research Site — Xi'an, China
Research Site — Xuzhou, China
Research Site — Yibin, China
Research Site — Aalborg, Denmark
Research Site — Herlev, Denmark
Research Site — København Ø, Denmark
Research Site — Odense, Denmark
Research Site — Helsinki, Finland
Research Site — Oulu, Finland
Research Site — Tampere, Finland
Research Site — Turku, Finland
Research Site — Besançon, France
Research Site — Bordeaux, France
Research Site — Caen, France
Research Site — Clermont-Ferrand, France
Research Site — Lyon, France
Research Site — Montpellier, France
Research Site — Nice, France
Research Site — Paris, France
Research Site — Plérin, France
Research Site — Poitiers, France
Research Site — Saint-Herblain, France
Research Site — Toulouse, France
Research Site — Berlin, Germany
Research Site — Chemnitz, Germany
Research Site — Dessau, Germany
Research Site — Dresden, Germany
Research Site — Düsseldorf, Germany
Research Site — Essen, Germany
Research Site — Hamburg, Germany
Research Site — Kassel, Germany
Research Site — Kiel, Germany
Research Site — Leipzig, Germany
Research Site — Mannheim, Germany
Research Site — Marburg, Germany
Research Site — München, Germany
Research Site — Münster, Germany
Research Site — Saarbrücken, Germany
Research Site — Budapest, Hungary
Research Site — Budapest, Hungary
Research Site — Debrecen, Hungary
Research Site — Catania, Italy
Research Site — Florence, Italy
Research Site — Milan, Italy
Research Site — Milan, Italy
Research Site — Milan, Italy
Research Site — Monza, Italy
Research Site — Naples, Italy
Research Site — Reggio Emilia, Italy
Research Site — Roma, Italy
Research Site — Rome, Italy
Research Site — Torino, Italy
Research Site — Turin, Italy
Research Site — Akashi-shi, Japan
Research Site — Ginowan-shi, Japan
Research Site — Hidaka-shi, Japan
Research Site — Isehara-shi, Japan
Research Site — Kashiwa, Japan
Research Site — Kashiwa-shi, Japan
Research Site — Kobe, Japan
Research Site — Kōtoku, Japan
Research Site — Kurume-shi, Japan
Research Site — Matsuyama, Japan
Research Site — Morioka, Japan
Research Site — Nagoya, Japan
Research Site — Niigata, Japan
Research Site — Osaka, Japan
Research Site — Ota-shi, Japan
Research Site — Sapporo, Japan
Research Site — Sendai, Japan
Research Site — Shinjuku-ku, Japan
Research Site — Sunto-gun, Japan
Research Site — Tokyo, Japan
Research Site — Yokohama, Japan
Research Site — Amsterdam, Netherlands
Research Site — Leiden, Netherlands
Research Site — Nijmegen, Netherlands
Research Site — Rotterdam, Netherlands
Research Site — Oslo, Norway
Research Site — Stavanger, Norway
Research Site — Bialystok, Poland
Research Site — Gdansk, Poland
Research Site — Lodz, Poland
Research Site — Poznan, Poland
Research Site — Siedlce, Poland
Research Site — Szczecin, Poland
Research Site — Goyang-si, South Korea
Research Site — Seoul, South Korea
Research Site — Seoul, South Korea
Research Site — Seoul, South Korea
Research Site — Seoul, South Korea
Research Site — Suwon, South Korea
Research Site — A Coruña, Spain
Research Site — Córdoba, Spain
Research Site — Donostia / San Sebastian, Spain
Research Site — El Palmar, Spain
Research Site — L'Hospitalet de Llobregat, Spain
Research Site — Madrid, Spain
Research Site — Madrid, Spain
Research Site — Palma de Mallorca, Spain
Research Site — Valencia, Spain
Research Site — Valencia, Spain
Research Site — Zaragoza, Spain
Research Site — Linköping, Sweden
Research Site — Lund, Sweden
Research Site — Stockholm, Sweden
Research Site — Uppsala, Sweden
Research Site — Frauenfeld, Switzerland
Research Site — Liestal, Switzerland
Research Site — Sankt Gallen, Switzerland
Research Site — Zurich, Switzerland
Research Site — Changhua, Taiwan
Research Site — Kaohsiung City, Taiwan
Research Site — New Taipei City, Taiwan
Research Site — Taichung, Taiwan
Research Site — Tainan, Taiwan
Research Site — Taipei, Taiwan
Research Site — Bath, United Kingdom
Research Site — Cambridge, United Kingdom
Research Site — Leeds, United Kingdom
Research Site — London, United Kingdom
Research Site — Manchester, United Kingdom
Research Site — Northwood, United Kingdom
Research Site — Taunton, United Kingdom

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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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