New treatment options for advanced endometrial cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

DESTINY-Endometrial01 is a Phase III clinical trial that evaluates the effectiveness of trastuzumab deruxtecan combined with either rilvegostomig or pembrolizumab as first-line treatments for patients with HER2-expressing endometrial cancer. The study compares these combinations against standard chemotherapy with carboplatin and paclitaxel plus pembrolizumab. The primary outcome measure is progression-free survival, assessed by independent central review in participants with advanced or recurrent disease. This trial aims to provide new therapeutic options for patients with specific cancer characteristics.

Why it matters

Who can join: the full rules

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.

Where it's running

• Research Site
  Little Rock, Arkansas, United States Recruiting
• Research Site
  Duarte, California, United States Recruiting
• Research Site
  Irvine, California, United States Recruiting
• Research Site
  La Jolla, California, United States Recruiting
• Research Site
  Fort Myers, Florida, United States Recruiting
• Research Site
  Miami Beach, Florida, United States Recruiting

+207 more sites. See ClinicalTrials.gov for the full list.

Study contacts

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

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• PF-08634404 plus chemotherapy in adults with advanced or recurrent pMMR endometrial cancer

  This study tests whether PF-08634404 added to standard chemotherapy helps adults with advanced or recurrent pMMR endometrial cancer more than pembrolizumab plus chemotherapy.

  Recruiting at 47 sites Phase 3 Pfizer · Jupiter, Florida and 53 other locations · NCT07578649

• Disitamab vedotin plus trastuzumab and tislelizumab versus chemotherapy plus trastuzumab (± pembrolizumab) for HER2‑high advanced gastric or gastroesophageal junction adenocarcinoma

  This trial tests whether combining disitamab vedotin with trastuzumab and the immunotherapy tislelizumab works better than standard chemotherapy with trastuzumab (with or without pembrolizumab) as first‑line treatment for people with HER2‑high advanced gastric or gastroesophageal junction cancer.

  Recruiting Phase 3 RemeGen Co., Ltd. · Beijing, BJ-Beijing · NCT07315750

• EIK1005 (Werner helicase inhibitor) alone or with pembrolizumab for advanced MSI-H/dMMR and other solid tumors

  This trial tests whether EIK1005, given alone or together with pembrolizumab, can be safely given and help people with advanced solid tumors, especially MSI‑H/dMMR cancers.

  Recruiting at 44 sites Phase 1/2 Eikon Therapeutics · Los Angeles, California and 44 other locations · NCT07262619

• BL-B01D1 plus pembrolizumab, with or without bevacizumab, for recurrent or metastatic cervical and endometrial cancer

  This trial will try a combination of BL-B01D1 and pembrolizumab, with or without bevacizumab, in adults with recurrent or metastatic cervical or endometrial cancer to see if it shrinks tumors or controls the disease.

  Recruiting Phase 2 Sichuan Baili Pharmaceutical Co., Ltd. · Shanghai, Shanghai Municipality · NCT07054567

• Trastuzumab deruxtecan versus standard chemotherapy for HER2-expressing (IHC 3+/2+) endometrial cancer

  This trial tests trastuzumab deruxtecan versus standard chemotherapy after surgery for adults with newly diagnosed HER2-expressing (IHC 3+/2+) endometrial cancer.

  Recruiting at 86 sites Phase 3 Daiichi Sankyo · Fort Lauderdale, Florida and 85 other locations · NCT07022483

• Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab alone for pMMR endometrial cancer

  This trial tests whether adding sacituzumab tirumotecan to pembrolizumab helps people with advanced or recurrent mismatch repair–proficient endometrial cancer live longer without their cancer getting worse compared to pembrolizumab alone.

  Recruiting at 266 sites Phase 3 Merck Sharp & Dohme LLC · Mobile, Alabama and 270 other locations · NCT06952504

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.