RECRUITING

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

Conditions

Breast Cancer Trastuzumab Derextecan Enhertu®DS8201-a Anti-HER2-Antibody Drug Conjugate

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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)

Quick Facts

Study Start:2023-12-30

Study Completion:2027-10-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05950945

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

(US Sites) Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

908-992-6400

CTRinfo@dsi.com

(Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

+81-3-6225-1111 (M-F 9-5 JST)

dsclinicaltrial@daiichisankyo.co.jp

Principal Investigator

Global Clinical Leader

STUDY_DIRECTOR

Daiichi Sankyo

Study Locations (Sites)

Mount Sinai Medical Center

Miami Beach, Florida, 33140

United States

USF College of Medicine

Tampa, Florida, 33602

United States

Beth Israel Lahey Health

Burlington, Massachusetts, 01805

United States

Collaborators and Investigators

Sponsor: Daiichi Sankyo

Global Clinical Leader, STUDY_DIRECTOR, Daiichi Sankyo

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-12-30

Study Completion Date2027-10-01

Study Record Updates

Study Start Date2023-12-30

Study Completion Date2027-10-01

Terms related to this study

Keywords Provided by Researchers

Trastuzumab Derextecan
Enhertu®
DS8201-a
Breast Cancer
Anti-HER2-Antibody Drug Conjugate

Additional Relevant MeSH Terms

Breast Cancer