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
DE-01
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
4 other identifiers
interventional
600
22 countries
246
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2025
Longer than P75 for phase_3
246 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 11, 2025
CompletedStudy Start
First participant enrolled
March 27, 2025
CompletedFirst Posted
Study publicly available on registry
May 25, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 19, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 19, 2031
May 6, 2026
May 1, 2026
3.8 years
March 11, 2025
May 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS), as assessed by BICR
Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause.
Until progression or death due to any cause (assessed up to approximately 45 months).
Secondary Outcomes (13)
Overall Survival (OS)
Until the date of death due to any cause (assessed up to approximately 70 months).
Progression Free Survival (PFS) as assessed by the investigator
Until progression or death due to any cause (assessed up to approximately 70 months).
Time from randomization to second progression or death (PFS2)
Until the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death (assessed up to approximately 70 months).
Objective response rate (ORR), as assessed by BICR and investigator
Until progression or the starting of subsequent anticancer therapy (assessed up to approximately 45 months).
Duration of response (DoR), as assessed by BICR and investigator
Until progression or death due to any cause (assessed up to approximately 45 months).
- +8 more secondary outcomes
Study Arms (3)
Arm A: T-DXd + Rilvegostomig
EXPERIMENTALT-DXd IV Q3W plus rilvegostomig IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first.
Arm B: T-DXd + Pembrolizumab
EXPERIMENTALT-DXd IV Q3W plus pembrolizumab IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first.
Arm C: Carboplatin + Paclitaxel + Pembrolizumab
ACTIVE COMPARATORCarboplatin, paclitaxel and pembrolizumab administered Q3W during 6 cycles, followed by maintenance with pembrolizumab IV Q6W during 14 cycles. Treatment with pembrolizumab will continue for up to 20 total cycles (approximately 24 months, accounting for combination and maintenance phases) or until other discontinuation criteria is met, whichever occurs first. At the discretion of the investigator, participants may continue to receive carboplatin, paclitaxel and pembrolizumab Q3W for up to 10 cycles. Docetaxel can be used as an alternative to paclitaxel for participants who had a hypersensitivity reaction to paclitaxel with a failed rechallenge (or not amenable to rechallenge), according to the investigator's clinical judgment.
Interventions
Experimental therapy by intravenous infusion
Immunotherapy by intravenous infusion
Standard of Care (SoC) chemotherapy by intravenous infusion
Standard of Care (SoC) chemotherapy by intravenous infusion
Standard of Care (SoC) chemotherapy by intravenous infusion
Eligibility Criteria
You may qualify if:
- 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.
- +1 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Daiichi Sankyo Co., Ltd.collaborator
- European Network for Gynaecological Oncological Trial groups(ENGOT)collaborator
- GOG Foundationcollaborator
Study Sites (250)
Research Site
Tucson, Arizona, 85704, United States
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Little Rock, Arkansas, 72205, United States
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Duarte, California, 91010, United States
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Irvine, California, 92618, United States
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La Jolla, California, 92037, United States
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Palo Alto, California, 94304, United States
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San Francisco, California, 94143, United States
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Sylmar, California, 91342, United States
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Fort Myers, Florida, 33901, United States
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Miami Beach, Florida, 33140, United States
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Orlando, Florida, 32804, United States
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St. Petersburg, Florida, 33705, United States
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Tampa, Florida, 33612, United States
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West Palm Beach, Florida, 33401, United States
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Augusta, Georgia, 30912, United States
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Honolulu, Hawaii, 96813, United States
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Arlington Heights, Illinois, 60005, United States
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Evanston, Illinois, 60201, United States
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Shreveport, Louisiana, 71103, United States
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Baltimore, Maryland, 21201, United States
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Boston, Massachusetts, 02111, United States
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Worcester, Massachusetts, 01655, United States
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Ann Arbor, Michigan, 48109, United States
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Detroit, Michigan, 48201, United States
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Minneapolis, Minnesota, 55455, United States
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Rochester, Minnesota, 55905, United States
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Jackson, Mississippi, 39216, United States
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Springfield, Missouri, 65804, United States
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St Louis, Missouri, 63141, United States
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Las Vegas, Nevada, 89169, United States
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Lebanon, New Hampshire, 03756, United States
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Hackensack, New Jersey, 07601, United States
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Albuquerque, New Mexico, 87109, United States
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New York, New York, 10016, United States
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New York, New York, 10065, United States
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New York, New York, 10075, United States
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Charlotte, North Carolina, 28204, United States
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Charlotte, North Carolina, 28204, United States
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Winston-Salem, North Carolina, 27103, United States
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Winston-Salem, North Carolina, 27157, United States
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Cincinnati, Ohio, 45220, United States
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Columbus, Ohio, 43210, United States
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Oklahoma City, Oklahoma, 73104, United States
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Tulsa, Oklahoma, 74134, United States
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Eugene, Oregon, 97401, United States
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Abington, Pennsylvania, 19001, United States
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Hershey, Pennsylvania, 17033, United States
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Philadelphia, Pennsylvania, 19111, United States
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Pittsburgh, Pennsylvania, 15224, United States
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Providence, Rhode Island, 02905, United States
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Charleston, South Carolina, 29425, United States
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Sioux Falls, South Dakota, 57105, United States
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Austin, Texas, 78758, United States
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Fort Worth, Texas, 76104, United States
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Houston, Texas, 77030, United States
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San Antonio, Texas, 78240, United States
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Charlottesville, Virginia, 22908, United States
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Fairfax, Virginia, 22031, United States
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Seattle, Washington, 98133, United States
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Madison, Wisconsin, 53792, United States
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Blacktown, 2148, Australia
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East Melbourne, 3002, Australia
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Nedlands, 6009, Australia
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South Brisbane, 4101, Australia
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Innsbruck, 6020, Austria
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Linz, 4021, Austria
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Vienna, 1090, Austria
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Wein, 1130, Austria
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Anderlecht, 1070, Belgium
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Brussels, 1200, Belgium
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Charleroi, 6060, Belgium
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Ghent, 9000, Belgium
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Barretos, 14784-057, Brazil
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Belo Horizonte, 30130 100, Brazil
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Goiânia, 74000-000, Brazil
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Londrina, 86015-520, Brazil
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Porto Alegre, 90020-090, Brazil
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Porto Alegre, 90610000, Brazil
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Rio de Janeiro, 20220-410, Brazil
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Salvador, 41.950-610, Brazil
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São Paulo, 01246-000, Brazil
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São Paulo, 01317-001, Brazil
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São Paulo, 1409, Brazil
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Teresina, 64049-200, Brazil
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Calgary, Alberta, T2N 5G2, Canada
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Edmonton, Alberta, T6G 1Z2, Canada
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Winnipeg, Manitoba, R3E 0V9, Canada
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Halifax, Nova Scotia, B3H 2Y9, Canada
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London, Ontario, N6A 4L6, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Montreal, Quebec, H1T 2M4, Canada
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Montreal, Quebec, H2X 0A9, Canada
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Montreal, Quebec, H3G 1A4, Canada
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Québec, Quebec, G1J 1Z4, Canada
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Beijing, 100142, China
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Changchun, 130021, China
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Changsha, 410013, China
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Chengdu, 610041, China
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Chengdu, 610072, China
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Chongqing, 400030, China
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Fuzhou, 350001, China
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Fuzhou, 350014, China
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Guangzhou, 510060, China
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Guangzhou, 510080, China
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Guangzhou, 510120, China
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Haikou, 570311, China
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Hangzhou, 310022, China
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Harbin, 150049, China
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Hefei, 230001, China
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Jinan, 250021, China
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Jinan, 250117, China
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Jining, 272029, China
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Kunming, 650118, China
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Lanzhou, 730030, China
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Nanchang, 330006, China
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Nanning, 530021, China
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Shanghai, 200011, China
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Shanghai, 201318, China
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Shantou, China
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Shenyang, 110004, China
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Shenyang, 110042, China
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Taiyuan, 030001, China
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Tianjin, 300060, China
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Ürümqi, 830000, China
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Wuhan, 430000, China
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Wuhan, 430022, China
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Xi'an, 710061, China
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Xuzhou, 221009, China
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Yibin, 610500, China
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Aalborg, 9100, Denmark
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Herlev, 2730, Denmark
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København Ø, 2100, Denmark
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Odense, 5000, Denmark
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Helsinki, 00290, Finland
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Oulu, 90029, Finland
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Tampere, 33520, Finland
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Turku, 20521, Finland
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Besançon, 25030, France
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Bordeaux, 33076, France
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Caen, 14076, France
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Clermont-Ferrand, 63000, France
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Lyon, 69373, France
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Montpellier, 34298, France
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Nice, 06100, France
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Paris, 75015, France
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Plérin, 22190, France
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Poitiers, 86021, France
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Saint-Herblain, 44805, France
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Toulouse, 31059, France
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Berlin, 13353, Germany
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Chemnitz, 09116, Germany
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Dessau, 06847, Germany
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Dresden, 01307, Germany
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Essen, 45147, Germany
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Hamburg, 20246, Germany
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Kassel, 34125, Germany
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Leipzig, 04103, Germany
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Mannheim, 68167, Germany
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Marburg, 35043, Germany
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Münster, 48149, Germany
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Saarbrücken, 66113, Germany
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Budapest, 1088, Hungary
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Budapest, 1122, Hungary
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Debrecen, 4032, Hungary
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Catania, 95100, Italy
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Florence, 50134, Italy
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Milan, 20141, Italy
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Milan, 20159, Italy
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Milan, 20162, Italy
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Monza, 20900, Italy
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Naples, 80131, Italy
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Reggio Emilia, 422122, Italy
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Roma, 00144, Italy
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Rome, 00168, Italy
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Torino, 10128, Italy
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Turin, 10128, Italy
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Akashi-shi, 673-8558, Japan
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Ginowan-shi, 901-2725, Japan
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Hidaka-shi, 350-1298, Japan
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Isehara-shi, 259-1193, Japan
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Kashiwa, 227-8577, Japan
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Kashiwa-shi, 277-8567, Japan
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Kobe, 650-0047, Japan
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Kōtoku, 135-8550, Japan
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Kurume-shi, 830-0011, Japan
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Matsuyama, 791-0280, Japan
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Morioka, 028-3695, Japan
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Nagoya, 464-8681, Japan
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Niigata, 951-8520, Japan
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Osaka, 541-8567, Japan
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Ota-shi, 373-8550, Japan
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Sapporo, 060-8638, Japan
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Sendai, 980-8574, Japan
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Shinjuku-ku, 160-8582, Japan
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Sunto-gun, 411-8777, Japan
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Tokyo, 104-0045, Japan
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Yokohama, 241-8515, Japan
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Amsterdam, 1066CX, Netherlands
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Leiden, 2333 ZA, Netherlands
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Nijmegen, 6525 GA, Netherlands
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Rotterdam, 3015 GD, Netherlands
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Oslo, 0379, Norway
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Stavanger, 4011, Norway
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Bialystok, 15-027, Poland
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Gdansk, 80-214, Poland
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Lodz, 93-338, Poland
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Poznan, 60-569, Poland
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Siedlce, 08-110, Poland
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Szczecin, 70-111, Poland
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Goyang-si, 10408, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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Suwon, 16499, South Korea
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A Coruña, 15009, Spain
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Córdoba, 14004, Spain
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Donostia / San Sebastian, 20014, Spain
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El Palmar, 30120, Spain
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L'Hospitalet de Llobregat, 08908, Spain
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Madrid, 28034, Spain
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Madrid, 28041, Spain
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Palma de Mallorca, 07010, Spain
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Valencia, 46006, Spain
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Valencia, 46009, Spain
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Zaragoza, 50009, Spain
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Linköping, 581 85, Sweden
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Lund, 22185, Sweden
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Stockholm, 17164, Sweden
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Uppsala, 751 85, Sweden
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Frauenfeld, 8501, Switzerland
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Liestal, CH- 4410, Switzerland
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Sankt Gallen, 9007, Switzerland
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Zurich, 8091, Switzerland
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Changhua, 500, Taiwan
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Kaohsiung City, 81362, Taiwan
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New Taipei City, 220, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 704, Taiwan
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Taipei, 10449, Taiwan
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Bath, BA1 3NG, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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London, EC1A 7BE, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Northwood, HA6 2RN, United Kingdom
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Taunton, TA1 5DA, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- This is an open-label, Sponsor-blinded study. To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment arm prior to final data readout for the primary endpoint.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 11, 2025
First Posted
May 25, 2025
Study Start
March 27, 2025
Primary Completion (Estimated)
January 19, 2029
Study Completion (Estimated)
February 19, 2031
Last Updated
May 6, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.