Tests trastuzumab deruxtecan in breast cancer with low or no HER2

Trial details

Who runs it

Daiichi Sankyo

Trial code

NCT05950945EU 2023-505616-38-00

Record updated

12 June 2026

Original description

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.Read full original descriptionShow less

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)

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.

Inclusion: 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: Prior treatment with an antibody drug conjugate (ADC); 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; Prior complete pneumonectomy; Uncontrolled or significant cardiovascular disease; 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 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; Lung-specific intercurrent clinically significant illnesses; Any autoimmune, connective tissue, or inflammatory disorders; Has a corrected QT interval prolongation; Has spinal cord compression or clinically active central nervous system metastases; Is pregnant or breastfeeding or planning to become pregnant.

ClinicalTrials.gov NCT05950945 · EU CTIS 2023-505616-38-00