Tests trastuzumab deruxtecan with immunotherapy for HER2-expressing endometrial cancer

Trial details

Who runs it

AstraZeneca

Trial code

NCT06989112EU 2023-508056-19-00

Record updated

13 October 2026

Original 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.Read full original descriptionShow less

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.

Inclusion: ≥ 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:; 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 (per FIGO 2023) disease regardless of presence of measurable disease at baseline; 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:; 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; No prior exposure to antibody-drug conjugates or immune checkpoint inhibitors; Participants may have received prior radiation therapy for the treatment of endometrial cancer. Adequate treatment washout period is required; 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.

Exclusion: Active or prior documented autoimmune or inflammatory disorders requiring chronic systemic treatment with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs; 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, 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); 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; 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; 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; History of organ transplant or allogeneic stem cell transplant; Evidence of any of the following infections:; Active tuberculosis; HIV infection that is not well controlled; Active hepatitis B or C infection; Spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases may be included in the study.

ClinicalTrials.gov NCT06989112 · EU CTIS 2023-508056-19-00