Evaluating trastuzumab deruxtecan for patients with low HER2 metastatic breast 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

This study evaluates the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with unresectable and/or metastatic breast cancer that is either hormone receptor-negative or hormone receptor-positive with low HER2 expression. The primary endpoint is time to next treatment (TTNT), which measures how long patients benefit from the drug before requiring alternative therapies. Participants must provide a biopsy and have specific HER2 and hormone receptor status as defined by established guidelines.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Sign and date the main informed consent form
* Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion.
* Pathologically documented Breast Cancer (BC) tumor

  * Is unresectable and/or metastatic.
  * Is hormone receptor-negative or hormone receptor-positive.

    * Must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative.
  * Has confirmed HER2 IHC 1+ or IHC 2+/ISH- (HER2-low) status or HER2 IHC 0 status as determined according to ASCO CAP 2018 guidelines1 based on sample collected during Tissue Screening as described above.
  * Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per ASCO CAP guidelines).
  * Was never previously treated with anti-HER2 therapy in the metastatic setting.
* Has had at least one and up to two prior lines of therapy in the metastatic setting.

  * In participants with hormone receptor-positive HER2-low metastatic BC (Cohort 3):

    * Has recurrent disease \<2 years from the initiation of adjuvant ET OR
    * Has disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor OR
    * Has disease progression within the first 12 months of CDK4/6 in the first line metastatic setting
* Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging.
* Participants with brain metastases are allowed in the study. The brain lesion(s) should be small (\<2 cm), untreated, asymptomatic, not requiring urgent medical intervention, and are asymptomatic and clinically stable.
* Has an Eastern Cooperative Oncology Group performance status of 0 or 1.
* Has a minimum life expectancy of 12 weeks at Screening.
* Has a left ventricular ejection fraction ≥50% within 28 days before enrollment.
* Has adequate organ and bone marrow function within 28 days before enrollment.
* Has adequate treatment washout period before enrollment.
* Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception.

Exclusion Criteria:

* Prior treatment with an antibody drug conjugate (ADC).
* Uncontrolled or significant cardiovascular disease.
* Has a corrected QT interval prolongation.
* Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
* Has spinal cord compression or clinically active central nervous system metastases.
* Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral BC.
* Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
* Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
* Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
* Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
* Has history of receiving a live, attenuated vaccine (messenger RNA and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study drug.
* Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline.
* Is pregnant or breastfeeding or planning to become pregnant.
* Lung-specific intercurrent clinically significant illnesses.
* Any autoimmune, connective tissue, or inflammatory disorders.
* Prior complete pneumonectomy.

Where it's running

• Dana-Farber Cancer Institute
  Boston, Massachusetts, United States Recruiting
• Overlook Medical Center
  Summit, New Jersey, United States Recruiting
• Institut Jules Bordet
  Anderlecht, Belgium Recruiting
• GZA Ziekenhuizen
  Wilrijk, Belgium Recruiting
• Centro de Oncologia - Unidade Brasília - Hospital Sírio Libanês
  Brasília, Brazil Recruiting
• CIONC-Centro Integrado de Oncologia de Curitiba
  Curitiba, Brazil Recruiting

+38 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: (US Sites) Daiichi Sankyo Contact for Clinical Trial Information
• Email: CTRinfo@dsi.com
• Phone: 908-992-6400

Similar studies

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

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  Recruiting Phase 1/2 Tianjin Medical University Cancer Institute and Hospital · Tianjin, Tianjin Municipality · NCT07708194

• Dendritic Cell Vaccine with HER2-targeted Therapy or Nivolumab for Breast Cancer with Leptomeningeal Metastasis

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• Brain metastases from breast cancer: see how trastuzumab deruxtecan in CSF relates to effect

  This study tests whether levels of trastuzumab deruxtecan in cerebrospinal fluid relate to how well it works for adults with breast cancer that has spread to the brain.

  Recruiting Fudan University · Shanghai, Shanghai Municipality · NCT07653893

• Trastuzumab Deruxtecan plus ivonescimab for HR+ HER2-low advanced breast cancer

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  Recruiting Phase 2 Fudan University · Shanghai, Shanghai Municipality · NCT07647016

• Pyrotinib and Trastuzumab with Dalpiciclib vs with Docetaxel in advanced HER2-positive breast cancer

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• Tucatinib with trastuzumab and capecitabine for HER2‑positive metastatic breast cancer in routine care

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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.