RecruitingPhase 3NCT05950945
Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer
A Phase 3b, Multicenter, Global, Interventional, Open-label Study of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-Antibody Drug Conjugate (ADC), in Subjects Who Have Unresectable and/or Metastatic HER2-low or HER2 Immunohistochemistry (IHC) 0 Breast Cancer (DESTINY-Breast15)
Sponsor
Daiichi Sankyo
Enrollment
250 participants
Start Date
Dec 30, 2023
Study Type
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Min Age: 18 Years
Inclusion Criteria22
- 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 Criteria16
- 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.
Interventions
DRUGTrastuzumab Deruxtecan
Intravenous administration, 5.4 mg/kg on Day 1 of each 21-day cycle until radiographic disease progression as assessed by the investigator, unacceptable toxicity, other discontinuation criteria are met, or 2 years after first dose of study drug
Locations(86)
View Full Details on ClinicalTrials.gov
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NCT05950945
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