Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer

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About the study

This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor \[HR\]-negative and HR-positive) unresectable and/or metastatic breast cancer.
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Who can take part

You may be eligible to participate in the study if you meet the following criteria:

INCLUSION CRITERIA

Inclusion Criteria:

  1. * Sign and date the main informed consent form
  2. * Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion.
  3. * Pathologically documented Breast Cancer (BC) tumor
  1. * Is unresectable and/or metastatic.
  2. * Is hormone receptor-negative or hormone receptor-positive.
  1. * Must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative.
  2. * 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.
  3. * Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per ASCO CAP guidelines).
  4. * Was never previously treated with anti-HER2 therapy in the metastatic setting.
  5. * 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):

  1. * Has recurrent disease \<2 years from the initiation of adjuvant ET OR
  2. * Has disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor OR
  3. * Has disease progression within the first 12 months of CDK4/6 in the first line metastatic setting
  4. * Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging.
  5. * 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.
  6. * Has an Eastern Cooperative Oncology Group performance status of 0 or 1.
  7. * Has a minimum life expectancy of 12 weeks at Screening.
  8. * Has a left ventricular ejection fraction ≥50% within 28 days before enrollment.
  9. * Has adequate organ and bone marrow function within 28 days before enrollment.
  10. * Has adequate treatment washout period before enrollment.
  11. * Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception.

EXCLUSION CRITERIA

Exclusion Criteria:

  1. * Prior treatment with an antibody drug conjugate (ADC).
  2. * Uncontrolled or significant cardiovascular disease.
  3. * Has a corrected QT interval prolongation.
  4. * 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.
  5. * Has spinal cord compression or clinically active central nervous system metastases.
  6. * 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.
  7. * Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
  8. * Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
  9. * Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
  10. * Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
  11. * 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.
  12. * Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline.
  13. * Is pregnant or breastfeeding or planning to become pregnant.
  14. * Lung-specific intercurrent clinically significant illnesses.
  15. * Any autoimmune, connective tissue, or inflammatory disorders.
  16. * Prior complete pneumonectomy.
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Study Locations

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How to Apply


Contact the study center to learn if this study is a good match for you.
Phone iconCall 908-992-6400Email iconEmail Study Center

Study Details


Contition
Breast Cancer
Age (in years)
18+
Phase
PHASE3
Participants Needed
250
Est. Completion Date
Oct 1, 2027
Treatment Type
INTERVENTIONAL

Sponsor
Daiichi Sankyo
ClinicalTrials.gov NCT Identifier
NCT05950945
Study Number
DS8201-0001-CIS-MA

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