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)

May 5, 2026 updated by: AstraZeneca

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

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.

Study Overview

Status

Recruiting

Conditions

Endometrial Cancer

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

600

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: AstraZeneca Clinical Study Information Center
Phone Number: 1-877-240-9479
Email: information.center@astrazeneca.com

Study Locations

Australia
- - Blacktown, Australia, 2148
    - Recruiting
    - Research Site
  - East Melbourne, Australia, 3002
    - Recruiting
    - Research Site
  - Nedlands, Australia, 6009
    - Recruiting
    - Research Site
  - South Brisbane, Australia, 4101
    - Recruiting
    - Research Site
Austria
- - Innsbruck, Austria, 6020
    - Not yet recruiting
    - Research Site
  - Linz, Austria, 4021
    - Not yet recruiting
    - Research Site
  - Vienna, Austria, 1090
    - Not yet recruiting
    - Research Site
  - Wein, Austria, 1130
    - Not yet recruiting
    - Research Site
Belgium
- - Anderlecht, Belgium, 1070
    - Not yet recruiting
    - Research Site
  - Brussels, Belgium, 1200
    - Recruiting
    - Research Site
  - Charleroi, Belgium, 6060
    - Withdrawn
    - Research Site
  - Ghent, Belgium, 9000
    - Recruiting
    - Research Site
  - Leuven, Belgium, 3000
    - Recruiting
    - Research Site
  - Liège, Belgium, 4000
    - Recruiting
    - Research Site
Brazil
- - Barretos, Brazil, 14784-057
    - Recruiting
    - Research Site
  - Belo Horizonte, Brazil, 30130 100
    - Recruiting
    - Research Site
  - Goiânia, Brazil, 74000-000
    - Recruiting
    - Research Site
  - Londrina, Brazil, 86015-520
    - Recruiting
    - Research Site
  - Porto Alegre, Brazil, 90020-090
    - Recruiting
    - Research Site
  - Porto Alegre, Brazil, 90610000
    - Recruiting
    - Research Site
  - Rio de Janeiro, Brazil, 20220-410
    - Recruiting
    - Research Site
  - Salvador, Brazil, 41.950-610
    - Recruiting
    - Research Site
  - São Paulo, Brazil, 01246-000
    - Recruiting
    - Research Site
  - São Paulo, Brazil, 01317-001
    - Recruiting
    - Research Site
  - São Paulo, Brazil, 1409
    - Recruiting
    - Research Site
  - Teresina, Brazil, 64049-200
    - Recruiting
    - Research Site
Canada
- Alberta
  - Calgary, Alberta, Canada, T2N 5G2
    - Recruiting
    - Research Site
  - Edmonton, Alberta, Canada, T6G 1Z2
    - Recruiting
    - Research Site
- Manitoba
  - Winnipeg, Manitoba, Canada, R3E 0V9
    - Withdrawn
    - Research Site
- Nova Scotia
  - Halifax, Nova Scotia, Canada, B3H 2Y9
    - Withdrawn
    - Research Site
- Ontario
  - London, Ontario, Canada, N6A 4L6
    - Recruiting
    - Research Site
  - Toronto, Ontario, Canada, M4N 3M5
    - Recruiting
    - Research Site
  - Toronto, Ontario, Canada, M5G 2M9
    - Recruiting
    - Research Site
- Quebec
  - Montreal, Quebec, Canada, H1T 2M4
    - Recruiting
    - Research Site
  - Montreal, Quebec, Canada, H2X 0A9
    - Recruiting
    - Research Site
  - Montreal, Quebec, Canada, H3G 1A4
    - Recruiting
    - Research Site
  - Québec, Quebec, Canada, G1J 1Z4
    - Recruiting
    - Research Site
China
- - Beijing, China, 100142
    - Recruiting
    - Research Site
  - Changchun, China, 130021
    - Recruiting
    - Research Site
  - Changsha, China, 410013
    - Recruiting
    - Research Site
  - Chengdu, China, 610041
    - Recruiting
    - Research Site
  - Chengdu, China, 610072
    - Recruiting
    - Research Site
  - Chongqing, China, 400030
    - Recruiting
    - Research Site
  - Fuzhou, China, 350001
    - Recruiting
    - Research Site
  - Fuzhou, China, 350014
    - Recruiting
    - Research Site
  - Guangzhou, China, 510120
    - Recruiting
    - Research Site
  - Guangzhou, China, 510080
    - Recruiting
    - Research Site
  - Guangzhou, China, 510060
    - Recruiting
    - Research Site
  - Haikou, China, 570311
    - Recruiting
    - Research Site
  - Hangzhou, China, 310022
    - Recruiting
    - Research Site
  - Harbin, China, 150049
    - Recruiting
    - Research Site
  - Hefei, China, 230001
    - Recruiting
    - Research Site
  - Jinan, China, 250117
    - Recruiting
    - Research Site
  - Jinan, China, 250021
    - Recruiting
    - Research Site
  - Jining, China, 272029
    - Recruiting
    - Research Site
  - Kunming, China, 650118
    - Recruiting
    - Research Site
  - Lanzhou, China, 730030
    - Recruiting
    - Research Site
  - Nanchang, China, 330006
    - Withdrawn
    - Research Site
  - Nanning, China, 530021
    - Recruiting
    - Research Site
  - Shanghai, China, 200011
    - Recruiting
    - Research Site
  - Shanghai, China, 201318
    - Recruiting
    - Research Site
  - Shantou, China
    - Recruiting
    - Research Site
  - Shenyang, China, 110042
    - Recruiting
    - Research Site
  - Shenyang, China, 110004
    - Recruiting
    - Research Site
  - Taiyuan, China, 030001
    - Recruiting
    - Research Site
  - Tianjin, China, 300060
    - Recruiting
    - Research Site
  - Wuhan, China, 430022
    - Recruiting
    - Research Site
  - Wuhan, China, 430000
    - Recruiting
    - Research Site
  - Xi'an, China, 710061
    - Recruiting
    - Research Site
  - Xuzhou, China, 221009
    - Recruiting
    - Research Site
  - Yibin, China, 610500
    - Withdrawn
    - Research Site
  - Ürümqi, China, 830000
    - Withdrawn
    - Research Site
Denmark
- - Aalborg, Denmark, 9100
    - Not yet recruiting
    - Research Site
  - Herlev, Denmark, 2730
    - Withdrawn
    - Research Site
  - København Ø, Denmark, 2100
    - Not yet recruiting
    - Research Site
  - Odense, Denmark, 5000
    - Not yet recruiting
    - Research Site
Finland
- - Helsinki, Finland, 00290
    - Recruiting
    - Research Site
  - Oulu, Finland, 90029
    - Not yet recruiting
    - Research Site
  - Tampere, Finland, 33520
    - Recruiting
    - Research Site
  - Turku, Finland, 20521
    - Recruiting
    - Research Site
France
- - Besançon, France, 25030
    - Withdrawn
    - Research Site
  - Bordeaux, France, 33076
    - Not yet recruiting
    - Research Site
  - Caen, France, 14076
    - Recruiting
    - Research Site
  - Clermont-Ferrand, France, 63000
    - Recruiting
    - Research Site
  - Lyon, France, 69373
    - Recruiting
    - Research Site
  - Montpellier, France, 34298
    - Recruiting
    - Research Site
  - Nice, France, 06100
    - Recruiting
    - Research Site
  - Paris, France, 75015
    - Recruiting
    - Research Site
  - Plérin, France, 22190
    - Recruiting
    - Research Site
  - Poitiers, France, 86021
    - Recruiting
    - Research Site
  - Saint-Herblain, France, 44805
    - Not yet recruiting
    - Research Site
  - Toulouse, France, 31059
    - Recruiting
    - Research Site
Germany
- - Berlin, Germany, 13353
    - Not yet recruiting
    - Research Site
  - Chemnitz, Germany, 09116
    - Not yet recruiting
    - Research Site
  - Dessau, Germany, 06847
    - Not yet recruiting
    - Research Site
  - Dresden, Germany, 01307
    - Not yet recruiting
    - Research Site
  - Essen, Germany, 45147
    - Not yet recruiting
    - Research Site
  - Hamburg, Germany, 20246
    - Not yet recruiting
    - Research Site
  - Kassel, Germany, 34125
    - Not yet recruiting
    - Research Site
  - Leipzig, Germany, 04103
    - Not yet recruiting
    - Research Site
  - Mannheim, Germany, 68167
    - Not yet recruiting
    - Research Site
  - Marburg, Germany, 35043
    - Withdrawn
    - Research Site
  - Münster, Germany, 48149
    - Not yet recruiting
    - Research Site
  - Saarbrücken, Germany, 66113
    - Not yet recruiting
    - Research Site
Hungary
- - Budapest, Hungary, 1122
    - Recruiting
    - Research Site
  - Budapest, Hungary, 1088
    - Recruiting
    - Research Site
  - Debrecen, Hungary, 4032
    - Recruiting
    - Research Site
Italy
- - Catania, Italy, 95100
    - Recruiting
    - Research Site
  - Florence, Italy, 50134
    - Recruiting
    - Research Site
  - Milan, Italy, 20141
    - Recruiting
    - Research Site
  - Milan, Italy, 20159
    - Recruiting
    - Research Site
  - Milan, Italy, 20162
    - Recruiting
    - Research Site
  - Monza, Italy, 20900
    - Not yet recruiting
    - Research Site
  - Naples, Italy, 80131
    - Recruiting
    - Research Site
  - Reggio Emilia, Italy, 422122
    - Not yet recruiting
    - Research Site
  - Roma, Italy, 00144
    - Recruiting
    - Research Site
  - Rome, Italy, 00168
    - Recruiting
    - Research Site
  - Torino, Italy, 10128
    - Recruiting
    - Research Site
  - Turin, Italy, 10128
    - Recruiting
    - Research Site
Japan
- - Akashi-shi, Japan, 673-8558
    - Withdrawn
    - Research Site
  - Ginowan-shi, Japan, 901-2725
    - Recruiting
    - Research Site
  - Hidaka-shi, Japan, 350-1298
    - Recruiting
    - Research Site
  - Isehara-shi, Japan, 259-1193
    - Recruiting
    - Research Site
  - Kashiwa, Japan, 227-8577
    - Not yet recruiting
    - Research Site
  - Kashiwa-shi, Japan, 277-8567
    - Recruiting
    - Research Site
  - Kobe, Japan, 650-0047
    - Recruiting
    - Research Site
  - Kurume-shi, Japan, 830-0011
    - Recruiting
    - Research Site
  - Kōtoku, Japan, 135-8550
    - Recruiting
    - Research Site
  - Matsuyama, Japan, 791-0280
    - Recruiting
    - Research Site
  - Morioka, Japan, 028-3695
    - Recruiting
    - Research Site
  - Nagoya, Japan, 464-8681
    - Not yet recruiting
    - Research Site
  - Niigata, Japan, 951-8520
    - Recruiting
    - Research Site
  - Osaka, Japan, 541-8567
    - Recruiting
    - Research Site
  - Ota-shi, Japan, 373-8550
    - Recruiting
    - Research Site
  - Sapporo, Japan, 060-8638
    - Recruiting
    - Research Site
  - Sendai, Japan, 980-8574
    - Recruiting
    - Research Site
  - Shinjuku-ku, Japan, 160-8582
    - Recruiting
    - Research Site
  - Sunto-gun, Japan, 411-8777
    - Recruiting
    - Research Site
  - Tokyo, Japan, 104-0045
    - Recruiting
    - Research Site
  - Yokohama, Japan, 241-8515
    - Not yet recruiting
    - Research Site
Netherlands
- - Amsterdam, Netherlands, 1066CX
    - Withdrawn
    - Research Site
  - Leiden, Netherlands, 2333 ZA
    - Withdrawn
    - Research Site
  - Nijmegen, Netherlands, 6525 GA
    - Withdrawn
    - Research Site
  - Rotterdam, Netherlands, 3015 GD
    - Withdrawn
    - Research Site
Norway
- - Oslo, Norway, 0379
    - Recruiting
    - Research Site
  - Stavanger, Norway, 4011
    - Recruiting
    - Research Site
Poland
- - Bialystok, Poland, 15-027
    - Recruiting
    - Research Site
  - Gdansk, Poland, 80-214
    - Recruiting
    - Research Site
  - Lodz, Poland, 93-338
    - Recruiting
    - Research Site
  - Poznan, Poland, 60-569
    - Recruiting
    - Research Site
  - Siedlce, Poland, 08-110
    - Recruiting
    - Research Site
  - Szczecin, Poland, 70-111
    - Not yet recruiting
    - Research Site
South Korea
- - Goyang-si, South Korea, 10408
    - Recruiting
    - Research Site
  - Seoul, South Korea, 03080
    - Recruiting
    - Research Site
  - Seoul, South Korea, 06351
    - Recruiting
    - Research Site
  - Seoul, South Korea, 05505
    - Recruiting
    - Research Site
  - Seoul, South Korea, 03722
    - Recruiting
    - Research Site
  - Suwon, South Korea, 16499
    - Recruiting
    - Research Site
Spain
- - A Coruña, Spain, 15009
    - Recruiting
    - Research Site
  - Córdoba, Spain, 14004
    - Recruiting
    - Research Site
  - Donostia / San Sebastian, Spain, 20014
    - Recruiting
    - Research Site
  - El Palmar, Spain, 30120
    - Recruiting
    - Research Site
  - L'Hospitalet de Llobregat, Spain, 08908
    - Recruiting
    - Research Site
  - Madrid, Spain, 28034
    - Recruiting
    - Research Site
  - Madrid, Spain, 28041
    - Recruiting
    - Research Site
  - Palma de Mallorca, Spain, 07010
    - Not yet recruiting
    - Research Site
  - Valencia, Spain, 46009
    - Recruiting
    - Research Site
  - Valencia, Spain, 46006
    - Recruiting
    - Research Site
  - Zaragoza, Spain, 50009
    - Recruiting
    - Research Site
Sweden
- - Linköping, Sweden, 581 85
    - Recruiting
    - Research Site
  - Lund, Sweden, 22185
    - Recruiting
    - Research Site
  - Stockholm, Sweden, 17164
    - Recruiting
    - Research Site
  - Uppsala, Sweden, 751 85
    - Recruiting
    - Research Site
Switzerland
- - Frauenfeld, Switzerland, 8501
    - Withdrawn
    - Research Site
  - Liestal, Switzerland, CH- 4410
    - Recruiting
    - Research Site
  - Sankt Gallen, Switzerland, 9007
    - Recruiting
    - Research Site
  - Zurich, Switzerland, 8091
    - Not yet recruiting
    - Research Site
Taiwan
- - Changhua, Taiwan, 500
    - Recruiting
    - Research Site
  - Kaohsiung City, Taiwan, 81362
    - Recruiting
    - Research Site
  - New Taipei City, Taiwan, 220
    - Recruiting
    - Research Site
  - Taichung, Taiwan, 40705
    - Recruiting
    - Research Site
  - Tainan, Taiwan, 704
    - Recruiting
    - Research Site
  - Taipei, Taiwan, 10449
    - Recruiting
    - Research Site
United Kingdom
- - Bath, United Kingdom, BA1 3NG
    - Recruiting
    - Research Site
  - Cambridge, United Kingdom, CB2 0QQ
    - Recruiting
    - Research Site
  - Leeds, United Kingdom, LS9 7TF
    - Recruiting
    - Research Site
  - London, United Kingdom, EC1A 7BE
    - Recruiting
    - Research Site
  - Manchester, United Kingdom, M20 4BX
    - Recruiting
    - Research Site
  - Northwood, United Kingdom, HA6 2RN
    - Recruiting
    - Research Site
  - Taunton, United Kingdom, TA1 5DA
    - Not yet recruiting
    - Research Site
United States
- Arizona
  - Tucson, Arizona, United States, 85704
    - Withdrawn
    - Research Site
- Arkansas
  - Little Rock, Arkansas, United States, 72205
    - Recruiting
    - Research Site
- California
  - Duarte, California, United States, 91010
    - Not yet recruiting
    - Research Site
  - Irvine, California, United States, 92618
    - Not yet recruiting
    - Research Site
  - La Jolla, California, United States, 92037
    - Recruiting
    - Research Site
  - Palo Alto, California, United States, 94304
    - Withdrawn
    - Research Site
  - San Francisco, California, United States, 94143
    - Suspended
    - Research Site
  - Sylmar, California, United States, 91342
    - Withdrawn
    - Research Site
- Florida
  - Fort Myers, Florida, United States, 33901
    - Recruiting
    - Research Site
  - Miami Beach, Florida, United States, 33140
    - Recruiting
    - Research Site
  - Orlando, Florida, United States, 32804
    - Not yet recruiting
    - Research Site
  - St. Petersburg, Florida, United States, 33705
    - Recruiting
    - Research Site
  - Tampa, Florida, United States, 33612
    - Recruiting
    - Research Site
  - West Palm Beach, Florida, United States, 33401
    - Recruiting
    - Research Site
- Georgia
  - Augusta, Georgia, United States, 30912
    - Recruiting
    - Research Site
- Hawaii
  - Honolulu, Hawaii, United States, 96813
    - Withdrawn
    - Research Site
- Illinois
  - Arlington Heights, Illinois, United States, 60005
    - Recruiting
    - Research Site
  - Evanston, Illinois, United States, 60201
    - Recruiting
    - Research Site
- Louisiana
  - Shreveport, Louisiana, United States, 71103
    - Recruiting
    - Research Site
- Maryland
  - Baltimore, Maryland, United States, 21201
    - Recruiting
    - Research Site
- Massachusetts
  - Boston, Massachusetts, United States, 02111
    - Recruiting
    - Research Site
  - Worcester, Massachusetts, United States, 01655
    - Withdrawn
    - Research Site
- Michigan
  - Ann Arbor, Michigan, United States, 48109
    - Not yet recruiting
    - Research Site
  - Detroit, Michigan, United States, 48201
    - Withdrawn
    - Research Site
- Minnesota
  - Minneapolis, Minnesota, United States, 55455
    - Recruiting
    - Research Site
  - Rochester, Minnesota, United States, 55905
    - Not yet recruiting
    - Research Site
- Mississippi
  - Jackson, Mississippi, United States, 39216
    - Recruiting
    - Research Site
- Missouri
  - Springfield, Missouri, United States, 65804
    - Not yet recruiting
    - Research Site
  - St Louis, Missouri, United States, 63141
    - Recruiting
    - Research Site
- Nevada
  - Las Vegas, Nevada, United States, 89169
    - Withdrawn
    - Research Site
- New Hampshire
  - Lebanon, New Hampshire, United States, 03756
    - Recruiting
    - Research Site
- New Jersey
  - Hackensack, New Jersey, United States, 07601
    - Not yet recruiting
    - Research Site
- New Mexico
  - Albuquerque, New Mexico, United States, 87109
    - Not yet recruiting
    - Research Site
- New York
  - New York, New York, United States, 10065
    - Recruiting
    - Research Site
  - New York, New York, United States, 10075
    - Withdrawn
    - Research Site
  - New York, New York, United States, 10016
    - Withdrawn
    - Research Site
- North Carolina
  - Charlotte, North Carolina, United States, 28204
    - Recruiting
    - Research Site
  - Charlotte, North Carolina, United States, 28204
    - Not yet recruiting
    - Research Site
  - Winston-Salem, North Carolina, United States, 27103
    - Recruiting
    - Research Site
  - Winston-Salem, North Carolina, United States, 27157
    - Not yet recruiting
    - Research Site
- Ohio
  - Cincinnati, Ohio, United States, 45220
    - Recruiting
    - Research Site
  - Columbus, Ohio, United States, 43210
    - Not yet recruiting
    - Research Site
- Oklahoma
  - Oklahoma City, Oklahoma, United States, 73104
    - Not yet recruiting
    - Research Site
  - Tulsa, Oklahoma, United States, 74134
    - Withdrawn
    - Research Site
- Oregon
  - Eugene, Oregon, United States, 97401
    - Recruiting
    - Research Site
- Pennsylvania
  - Abington, Pennsylvania, United States, 19001
    - Withdrawn
    - Research Site
  - Hershey, Pennsylvania, United States, 17033
    - Withdrawn
    - Research Site
  - Philadelphia, Pennsylvania, United States, 19111
    - Recruiting
    - Research Site
  - Pittsburgh, Pennsylvania, United States, 15224
    - Recruiting
    - Research Site
- Rhode Island
  - Providence, Rhode Island, United States, 02905
    - Recruiting
    - Research Site
- South Carolina
  - Charleston, South Carolina, United States, 29425
    - Recruiting
    - Research Site
- South Dakota
  - Sioux Falls, South Dakota, United States, 57105
    - Recruiting
    - Research Site
- Texas
  - Austin, Texas, United States, 78758
    - Recruiting
    - Research Site
  - Fort Worth, Texas, United States, 76104
    - Recruiting
    - Research Site
  - Houston, Texas, United States, 77030
    - Recruiting
    - Research Site
  - San Antonio, Texas, United States, 78240
    - Recruiting
    - Research Site
- Virginia
  - Charlottesville, Virginia, United States, 22908
    - Recruiting
    - Research Site
  - Fairfax, Virginia, United States, 22031
    - Not yet recruiting
    - Research Site
- Washington
  - Seattle, Washington, United States, 98133
    - Withdrawn
    - Research Site
- Wisconsin
  - Madison, Wisconsin, United States, 53792
    - Recruiting
    - Research Site

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.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: T-DXd + Rilvegostomig T-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.	Drug: Trastuzumab deruxtecan Experimental therapy by intravenous infusion Other Names: DS-8201a, T-DXd Drug: Rilvegostomig Experimental therapy by intravenous infusion
Experimental: Arm B: T-DXd + Pembrolizumab T-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.	Drug: Trastuzumab deruxtecan Experimental therapy by intravenous infusion Other Names: DS-8201a, T-DXd Drug: Pembrolizumab Immunotherapy by intravenous infusion Other Names: Keytruda
Active Comparator: Arm C: Carboplatin + Paclitaxel + Pembrolizumab Carboplatin, 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.	Drug: Pembrolizumab Immunotherapy by intravenous infusion Other Names: Keytruda Drug: Carboplatin Standard of Care (SoC) chemotherapy by intravenous infusion Other Names: Carbomedac, Carbosin, Paraplatin Drug: Paclitaxel Standard of Care (SoC) chemotherapy by intravenous infusion Other Names: Anzatax, Ebetaxel, Oncotaxel, Paclitax, Paclitaxin, Paxene, Taxol Drug: Docetaxel Standard of Care (SoC) chemotherapy by intravenous infusion Other Names: Docirena, Taxceus, Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS), as assessed by BICR Time Frame: Until progression or death due to any cause (assessed up to approximately 45 months).	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) Time Frame: Until the date of death due to any cause (assessed up to approximately 70 months).	Defined as the time from randomization until the date of death due to any cause.	Until the date of death due to any cause (assessed up to approximately 70 months).
Progression Free Survival (PFS) as assessed by the investigator Time Frame: Until progression or death due to any cause (assessed up to approximately 70 months).	PFS by investigator has the same attributes as estimand of PFS by BICR except tumor assessment is 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) Time Frame: 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).	PFS2 will be defined as the time from randomization to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.	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 Time Frame: Until progression or the starting of subsequent anticancer therapy (assessed up to approximately 45 months).	ORR as assessed and confirmed by BICR is defined as the proportion of participants who have a complete response (CR) or partial response (PR), as determined and confirmed by BICR. ORR as assessed and confirmed by the investigator has the same attributes as estimand of ORR by BICR except tumor assessment per the 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 Time Frame: Until progression or death due to any cause (assessed up to approximately 45 months).	DoR as assessed by BICR will be defined as the time from the date of first documented response of confirmed responders until date of documented progression per RECIST 1.1, or death due to any cause. DoR as assessed by the investigator has the same attributes as estimand of DoR by BICR except tumor assessment per the investigator.	Until progression or death due to any cause (assessed up to approximately 45 months).
Safety and tolerability Time Frame: Safety is assessed until the 90 days (+7) after the last dose (assessed up to approximately 70 months).	Safety and tolerability will be evaluated in terms of AEs/serious AEs (SAEs), AESI, vital signs, clinical safety laboratory assessments, ECG and ECHO/MUGA scan results.	Safety is assessed until the 90 days (+7) after the last dose (assessed up to approximately 70 months).
Pharmacokinetics of T-DXd, total anti-HER2 antibody, DXd and rilvegostomig Time Frame: Up to safety follow-up period (assessed up to approximately 45 months).	Serum concentration of T-DXd, total anti-HER2 antibody, DXd and rilvegostomig.	Up to safety follow-up period (assessed up to approximately 45 months).
Immunogenicity of T- DXd and rilvegostomig Time Frame: Up to safety follow-up period (assessed up to approximately 45 months).	Presence of ADAs for T-DXd or rilvegostomig.	Up to safety follow-up period (assessed up to approximately 45 months).
Patient-reported tolerability Time Frame: Up to progression as assessed by BICR (assessed up to approximately 45 months).	Patient-reported tolerability will be described among participants, as treated, using the following outcomes: Symptomatic AEs: Descriptive summary of the proportion of participants reporting symptomatic AEs while on treatment, as assessed by items from the EORTC Item Library and the FACT/GOG-NTX-4 Overall side-effect bother: Descriptive summary of the proportion of participants reporting overall side-effect bother on the PGI-TT while on treatment	Up to progression as assessed by BICR (assessed up to approximately 45 months).
Progression-free survival (PFS) according to MMR status to determine the clinical utility of a MMR diagnostic test Time Frame: Through completion of study, assessed up to approximately 70 months.	PFS is defined as time from randomization until progression per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) as assessed by BICR, or death due to any cause.	Through completion of study, assessed up to approximately 70 months.
Overall survival (OS) according to MMR status to determine the clinical utility of a MMR diagnostic test Time Frame: Through completion of study, assessed up to approximately 70 months.	OS defined as the time from randomization until the date of death due to any cause.	Through completion of study, assessed up to approximately 70 months.
Progression-free survival (PFS) according to HER2 expression to determine the clinical utility of a HER2 diagnostic test Time Frame: Through completion of study, assessed up to approximately 70 months.	PFS is defined as time from randomization until progression per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) as assessed by BICR, or death due to any cause.	Through completion of study, assessed up to approximately 70 months.
Overall survival (OS) according to HER2 expression to determine the clinical utility of a HER2 diagnostic test Time Frame: Through completion of study, assessed up to approximately 70 months.	OS is defined as the time from randomization until the date of death due to any cause.	Through completion of study, assessed up to approximately 70 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Collaborators

GOG Foundation

Daiichi Sankyo Co., Ltd.

European Network for Gynaecological Oncological Trial groups(ENGOT)

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 Major Dates

Study Start (Actual)

March 27, 2025

Primary Completion (Estimated)

January 19, 2029

Study Completion (Estimated)

February 19, 2031

Study Registration Dates

First Submitted

March 11, 2025

First Submitted That Met QC Criteria

May 15, 2025

First Posted (Actual)

May 25, 2025

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

May 5, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

D781DC00001
2023-508056-19-00 (Registry Identifier: CTIS (EU))
GOG-3098 (Other Identifier: Gynecologic Oncology Group Foundation)
ENGOT-EN24 (Other Identifier: European Network for Gynaecological Oncological Trial groups)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

STUDY_PROTOCOL
SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Endometrial Cancer

Radboud University Medical Center
Maastricht University Medical Center; Erasmus Medical Center; Catharina Ziekenhuis... and other collaborators

Recruiting

PROMOTE Study: Prediction of Response Of HorMOnal Treatment in Advanced and Recurrent Endometrial Cancer (PROMOTE)

Endometrial Cancer Recurrent | Endometrial Cancer Stage III | Endometrial Cancer Stage IV

Netherlands
Assistance Publique - Hôpitaux de Paris
Université Montpellier; Ecole d'econmie de Paris (PSE)-Hospinnomics; Université...

Completed

Cost-utility of Ambulatory Surgery in the Management of Endometrial Cancer(AMBU-ENDO) (AMBU-ENDO)

Endometrial Cancer Stage I | Endometrial Cancer Stage II

France
Ain Shams Maternity Hospital

Not yet recruiting

Evaluation of Laparoscopic Staging Versus Staging Laparotomy for Early Stage Endometrial Cancer

Treatment Endometrial Cancer
Mayo Clinic

Recruiting

Molecular and ctDNA Characterization of High-Risk Endometrial Cancer

Endometrial Carcinoma | Stage III Endometrial Cancer | Stage IV Endometrial Cancer | Endometrial High Grade Endometrioid Adenocarcinoma | Stage II Endometrial Cancer

United States
Batman Training and Research Hospital
Eskisehir Osmangazi University

Completed

The Compatibility of Preoperative Endometrial Biopsies With Postoperative Final Pathology in Endometrial Cancer

Gynecologic Cancer | Endometrial Cancer Stage
Rambam Health Care Campus

Completed

P16 Staining as Prognostic Biomarker in Serous Papillary Endometrial Cancer

Serous Papillary Endometrial Cancer

Israel
University of Southern Denmark
Danish Cancer Society; Region of Southern Denmark

Recruiting

An Individualised and Patient-centred Follow-up Program for Women With Gynaecological Cancer (NEMO)

Empowerment, Cervical Cancer, Endometrial Cancer, Follow-up, Nurse-led, PROM

Denmark
Novartis Pharmaceuticals

Completed

BKM120 as Second-line Therapy for Advanced Endometrial Cancer

Advanced Endometrial Cancer

Belgium, France, Italy, Canada, Spain, Australia, Germany, United States, Japan, Brazil, Singapore, Russian Federation, Poland
Samsung Medical Center

Recruiting

Clinical Effects of Metformin on Fertility-sparing Treatment for Early Endometrial Cancer

Endometrial Cancer Stage I

Korea, Republic of
Duke University
Duke Cancer Institute

Completed

Endometrial Cancer Diet and Exercise

Early Stage Endometrial Cancer

United States

Clinical Trials on Trastuzumab deruxtecan

Wenjin Yin

Recruiting

Trastuzumab Deruxtecan in Advanced Breast Cancer

Advanced Breast Cancer

China
Memorial Sloan Kettering Cancer Center
AstraZeneca

Recruiting

A Study of Trastuzumab Deruxtecan in People With Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer | Non-Small Cell Lung Cancer Stage IIIB | Non-small Cell Lung Cancer Stage II | Non-Small Cell Lung Cancer Stage IIIA

United States, Canada
Henan Cancer Hospital

Not yet recruiting

Trastuzumab Rezetecan vs Trastuzumab Deruxtecan in the Neoadjuvant Treatment of HER2 Positive Breast Cancer

Breast Cancer
Fundación Pública Andaluza para la Investigación...

Recruiting

Impact of Genetic Variants on the Toxicity of Antibody-Drug Conjugates in Locally Advanced or Metastatic Breast Cancer: The Role of the UGT1A1 Gene as a Predictive Biomarker of Therapeutic Response

Breast Cancer | Metastatic Breast Cancer | Drug-Related Side Effects and Adverse Reactions | Pharmacogenetic Variant

Spain
Fudan University

Not yet recruiting

T-DXd With or Without Neratinib for HER2 Positive Breast Cancer With Brain Metastasis (THUNDER)

HER2-positive Breast Cancer | Breast Cancer With Brain Metastasis
Fudan University

Not yet recruiting

Sequencing SG vs. T-DXd in HER2-Low/TROP2-High Metastatic Breast Cancer (STORM)

Metastatic Breast Cancer
UNICANCER

Not yet recruiting

Testing Two Different Drugs (Sacituzumab-govitecan and Trastuzumab-deruxtecan) Combinations Prescribed in an Alterning Pattern to Patients With Metastatic or Locally Advanced Triple-negative Breast Cancer (ALTER)

Neoplasm Metastasis | Triple Negative Breast Neoplasms | HER 2 Low-expressing Breast Cancer

France
Sun Yat-sen University

Not yet recruiting

Megestrol Acetate for Fatigue Management in T-DXd Treated Breast Cancer (MEGA-TACT-BC3)

Advanced/Metastatic Breast Cancer | HER2+, Low, or Ultralow Advanced/Metastatic Breast Cancer

China
Sarah Sammons, MD
Stemline Therapeutics, Inc.

Recruiting

ERADICATE: A Phase Ib/II Study of Elacestrant Plus Trastuzumab Deruxtecan in Patients With CDK4/6 Inhibitor and Endocrine-resistant HR+/HER2-low or HER2-ultralow Metastatic Breast Cancer (ERADICATE)

Breast Cancer | Metastatic Breast Cancer | Breast Cancer Female | HER2-negative Breast Cancer | HER2 Low Breast Carcinoma

United States
Jiangsu HengRui Medicine Co., Ltd.

Recruiting

A Trial of Trastuzumab Rezetecan in Unresectable Locally Recurrent/Metastatic Breast Cancer

Unresectable Locally Recurrent Breast Cancer | Unresectable Locally Metastatic Breast Cancer

China

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)

Study Overview

Status

Conditions

Intervention / Treatment

Study Type

Enrollment (Estimated)

Phase

Contacts and Locations

Study Contact

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Collaborators

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Estimated)

Study Completion (Estimated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Actual)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

IPD Plan Description

IPD Sharing Time Frame

IPD Sharing Access Criteria

IPD Sharing Supporting Information Type

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

Clinical Trials on Endometrial Cancer

Clinical Trials on Trastuzumab deruxtecan

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tanzania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations