Recruiting
Phase 3

Trastuzumab Deruxtecan & Rilvegostomig

Sponsor:

AstraZeneca

Code:

NCT06989112

Conditions

Endometrial Cancer

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Trastuzumab deruxtecan

Rilvegostomig

Pembrolizumab

Carboplatin

Paclitaxel

Study Details

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.

Conditions

Endometrial Cancer

Study ID

NCT06989112

Start date

Mar 27, 2025

Status verified date

Sep, 2026

Completion date

Feb 19, 2031

Anticipated

Primary completion date

Jan 19, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

600 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

active comparator: Arm C: Carboplatin + Paclitaxel + Pembrolizumab

Carboplatin, paclitaxel and pembrolizumab administered Q3W for 6 cycles, followed by maintenance with pembrolizumab IV Q6W for 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

Trastuzumab deruxtecan

Experimental therapy by intravenous infusion

Rilvegostomig

Experimental therapy by intravenous infusion

Pembrolizumab

Immunotherapy by intravenous infusion

Carboplatin

Standard of Care (SoC) chemotherapy by intravenous infusion

Paclitaxel

Standard of Care (SoC) chemotherapy by intravenous infusion

Docetaxel

Standard of Care (SoC) chemotherapy by intravenous infusion

Primary outcome measure

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

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Little Rock, Arkansas, United States, 72205

Research Site

Recruiting

Duarte, California, United States, 91010

Research Site

Recruiting

Irvine, California, United States, 92618

Research Site

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La Jolla, California, United States, 92037

Research Site

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Fort Myers, Florida, United States, 33901

Research Site

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Miami Beach, Florida, United States, 33140

Research Site

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St. Petersburg, Florida, United States, 33705

Research Site

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Tampa, Florida, United States, 33612

Research Site

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West Palm Beach, Florida, United States, 33401

Research Site

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Arlington Heights, Illinois, United States, 60005

Research Site

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Evanston, Illinois, United States, 60201

Research Site

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Shreveport, Louisiana, United States, 71103

Research Site

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Baltimore, Maryland, United States, 21201

Research Site

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Boston, Massachusetts, United States, 02111

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Ann Arbor, Michigan, United States, 48109

Research Site

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Minneapolis, Minnesota, United States, 55455

Research Site

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Rochester, Minnesota, United States, 55905

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Jackson, Mississippi, United States, 39216

Research Site

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Springfield, Missouri, United States, 65804

Research Site

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St Louis, Missouri, United States, 63141

Research Site

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Lebanon, New Hampshire, United States, 03756

Research Site

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Hackensack, New Jersey, United States, 07601

Research Site

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New York, New York, United States, 10065

Research Site

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Charlotte, North Carolina, United States, 28204

Research Site

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Winston-Salem, North Carolina, United States, 27103

Research Site

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Cincinnati, Ohio, United States, 45220

Research Site

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Columbus, Ohio, United States, 43210

Research Site

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Eugene, Oregon, United States, 97401

Research Site

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Philadelphia, Pennsylvania, United States, 19111

Research Site

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Pittsburgh, Pennsylvania, United States, 15224

Research Site

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Providence, Rhode Island, United States, 02905

Research Site

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Charleston, South Carolina, United States, 29425

Research Site

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Sioux Falls, South Dakota, United States, 57105

Research Site

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Austin, Texas, United States, 78758

Research Site

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Fort Worth, Texas, United States, 76104

Research Site

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Houston, Texas, United States, 77030

Research Site

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San Antonio, Texas, United States, 78240

Research Site

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Charlottesville, Virginia, United States, 22908

Research Site

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Fairfax, Virginia, United States, 22031

Research Site

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Madison, Wisconsin, United States, 53792

Research Site

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Calgary, Alberta, Canada, T2N 5G2

Research Site

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Research Site

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London, Ontario, Canada, N6A 4L6

Research Site

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Research Site

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Toronto, Ontario, Canada, M5G 2M9

Research Site

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Montreal, Quebec, Canada, H1T 2M4

Research Site

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Montreal, Quebec, Canada, H2X 0A9

Research Site

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Montreal, Quebec, Canada, H3G 1A4

Research Site

Recruiting

Québec, Quebec, Canada, G1J 1Z4

More Information

Sponsor

AstraZeneca

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Keywords

  • Endometrial Cancer
  • Uterine Cancer
  • Endometrial Carcinoma
  • Human epidermal growth factor receptor 2 (HER2)
  • pMMR
  • Trastuzumab deruxtecan
  • T-DXd
  • 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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-09-03.