A study to find out how well T-DXd works in combination with immunotherapy compared to chemotherapy in combination with immunotherapy in adults with advanced or recurrent HER2-expressing pMMR endometrial cancer
Résumé de l'étude
Researchers are looking for a better way to treat advanced or recurrent HER2-expressing pMMR endometrial cancer (uterine cancer). In people with endometrial cancer, the body is unable to control the growth of some cells in the endometrium. The endometrium is the lining of the uterus. The additional cells can form tumors that can impair the normal function of organs and the body.
This clinical study investigates a new treatment for patients with advanced or recurrent endometrial cancer with high HER2 expression and functioning mismatch repair system (pMMR). There are currently limited treatment options for this type of cancer, and the outlook is often poor.
The study compares three treatment groups: two groups receive a novel combination therapy – either Trastuzumab Deruxtecan (T-DXd) together with Rilvegostomig or T-DXd together with Pembrolizumab, both of which are specific immunotherapies. The third group receives the current standard therapy, which is chemotherapy (Carboplatin and Paclitaxel) together with Pembrolizumab.
Chemotherapies generally attack all rapidly dividing cells, while the new therapeutic approaches specifically target cancer cells and activate the immune system or destroy tumor cells from within. The aim of the study is to find out whether the new combinations are better suited to prevent cancer progression and maintain quality of life than the current standard treatment.
(BASEC)
Intervention étudiée
This study examines Trastuzumab Deruxtecan (T-DXd), a so-called antibody-drug conjugate, in combination with other immunotherapies (Rilvegostomig or Pembrolizumab) compared to standard therapy (chemotherapy plus Pembrolizumab).
Participants are randomly assigned to 3 treatment groups:
Group 1 receives T-DXd with Rilvegostomig. Group 2 receives T-DXd with Pembrolizumab, and Group 3 receives chemotherapy with Pembrolizumab.
All groups will be treated every 3 weeks. After a treatment phase of 18 to 30 weeks, changes to the treatment plan may be made for participants in Group 3, depending on what the investigators believe is best for the participants.
What is Trastuzumab Deruxtecan (T-DXd)?
T-DXd is a “targeted” cancer drug that specifically recognizes and attacks cancer cells with a high amount of the HER2 protein. The active substance consists of two components: on one hand, an antibody (Trastuzumab) that specifically binds to the HER2 protein on the surface of the tumor cell. On the other hand, the antibody carries a cytotoxic agent (Deruxtecan) that is directly delivered into the cancer cell. Once inside the tumor cell, the cytotoxic agent is released and leads to the death of the cancer cell. The goal of this therapy is to damage as many tumor cells as possible while harming as few healthy cells as possible.
Rilvegostomig and Pembrolizumab – Immunotherapies
Both substances belong to the so-called immune checkpoint inhibition. These drugs help the body's immune system to better recognize and fight cancer cells by removing “brakes” on immune cells. Rilvegostomig targets two different brakes (PD-1 and TIGIT), while Pembrolizumab targets one (PD-1). Such drugs can strengthen the body's defense against the tumor and remove its camouflage.
Comparison treatment
The control group receives standard chemotherapy (Carboplatin plus Paclitaxel) in combination with Pembrolizumab, which is considered the current standard treatment for advanced or recurrent endometrial cancer in many countries.
The aim of the study is to find out whether T-DXd in combination with Rilvegostomig or Pembrolizumab works better and is well tolerated compared to standard treatment.
(BASEC)
Maladie en cours d'investigation
Endometrial cancer (uterine cancer) with HER2 overexpression and intact mismatch repair system (pMMR), advanced or recurrent:
Endometrial cancer is a type of cancer that arises in the lining of the uterus (endometrium). The endometrium is the inner lining of the uterus. When control over cell growth in the lining is lost, tumors can form. These tumors can spread to other organs, impairing function, and in the case of advanced disease, they can no longer be cured by surgery. A recurrence means that the cancer reappears after previous treatment.
This study particularly examines a group of patients whose tumor exhibits a high occurrence of the HER2 protein (“HER2-expressing,” i.e., immunohistochemistry IHC 3+ or 2+). This form of the tumor usually grows more aggressively. Another feature is the so-called “proficient mismatch repair” (pMMR): This means that the cell's own repair system for genetic protection still functions in these tumor cells. This biological property influences how a tumor responds to therapies.
Endometrial cancer is the second most common gynecological cancer worldwide after breast cancer. Unfortunately, advanced or recurrent cases often have a poor prognosis, especially when standard therapies such as surgery and chemotherapy are not sufficiently effective. New treatment approaches and better therapies are urgently needed, especially for patients with HER2-expressing, pMMR endometrial cancer.
(BASEC)
- Adult patients (≥ 18 years) with primarily advanced (stage III/IV) or first recurrence of endometrial cancer, where the disease can no longer be cured by surgery.
- Confirmed high expression of the HER2 protein in the tumor through central laboratory tests (immunohistochemistry 3+ or 2+) and intact function of the mismatch repair system (pMMR status, meaning no deficiency of repair proteins in the tumor).
- No previous systemic first-line therapy for advanced or recurrent endometrial cancer.
(BASEC)
Critères d'exclusion
- Pre-existing or active pneumonia/interstitial lung disease (ILD/pneumonitis) that requires treatment.
- Active or known autoimmune disease that excludes treatment with immunotherapies.
- Known, inadequately treated, or unexplained dysfunction of important organs (e.g., severe liver or kidney failure, severe heart failure, or uncontrolled infections such as hepatitis B/C, HIV).
(BASEC)
Lieu de l’étude
Bâle, Zurich
(BASEC)
Sponsor
AstraZeneca AG
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Clinical Trials Schweiz
+41 41 725 75 75
clinical-trials@clutterastrazeneca.comAstraZeneca AG
(BASEC)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Ethikkommission Nordwest- und Zentralschweiz EKNZ
(BASEC)
Date d'approbation du comité d'éthique
29.10.2025
(BASEC)
Identifiant de l'essai ICTRP
NCT06989112 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
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 (BASEC)
Titre académique
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 (ICTRP)
Titre public
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 (ICTRP)
Maladie en cours d'investigation
Endometrial Cancer
(ICTRP)
Intervention étudiée
Drug: Trastuzumab deruxtecanDrug: RilvegostomigDrug: PembrolizumabDrug: CarboplatinDrug: PaclitaxelDrug: Docetaxel
(ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
(ICTRP)
Critères d'inclusion/exclusion
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.
(ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Progression-free survival (PFS), as assessed by BICR
(ICTRP)
Duration of response (DoR), as assessed by BICR and investigator;Overall Survival (OS);Progression Free Survival (PFS) as assessed by the investigator;Time from randomization to second progression or death (PFS2);Objective response rate (ORR), as assessed by BICR and investigator;Safety and tolerability;Pharmacokinetics of T-DXd, total anti-HER2 antibody, DXd and rilvegostomig;Immunogenicity of T- DXd and rilvegostomig;Patient-reported tolerability;Progression-free survival (PFS) according to MMR status to determine the clinical utility of a MMR diagnostic test;Overall survival (OS) according to MMR status to determine the clinical utility of a MMR diagnostic test;Progression-free survival (PFS) according to HER2 expression to determine the clinical utility of a HER2 diagnostic test;Overall survival (OS) according to HER2 expression to determine the clinical utility of a HER2 diagnostic test
(ICTRP)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
Daiichi Sankyo Co., Ltd.;GOG Foundation;European Network of Gynaecological Oncological Trial Groups (ENGOT) (ICTRP)
Contacts supplémentaires
AstraZeneca Clinical Study Information Center, information.center@astrazeneca.com, 1-877-240-9479 (ICTRP)
ID secondaires
2023-508056-19-00, GOG-3098, ENGOT-EN24, D781DC00001 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT06989112 (ICTRP)
Résultats de l'essai
Résumé des résultats
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Lien vers les résultats dans le registre primaire
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