Recruiting
Phase 3

Trastuzumab Deruxtecan

Sponsor:

Daiichi Sankyo

Code:

NCT05950945

Conditions

Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Trastuzumab Deruxtecan

Study Details

Brief 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.

Conditions

Breast Cancer

Study ID

NCT05950945

Start date

Dec 30, 2023

Status verified date

Jun, 2026

Completion date

Oct 1, 2027

Anticipated

Primary completion date

Oct 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

250 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort 1: HR-negative, HER2-low

Participants with HR-negative HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.

experimental: Cohort 2: HR-negative, HER2 IHC 0

Participants with HR-negative HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.

experimental: Cohort 3: HR-positive, HER2-low

Participants with HR-positive HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.

Participants must also have recurrent disease <2 years from the initiation of adjuvant ET or have disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor or have disease progression within the first 12 months of CDK4/6 in the first line metastatic setting.

experimental: Cohort 4: HR-positive, HER2 IHC 0

Participants with HR-positive HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.

Interventions

Trastuzumab 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

Primary outcome measure

  • Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT) [ Time Frame: Until subsequent therapy or death, assessed up to 24 months ]

Central Contacts and Locations

Central contacts

(US Sites) Daiichi Sankyo Contact for Clinical Trial Information

908-992-6400CTRinfo@dsi.com

(Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information

+81-3-6225-1111 (M-F 9-5 JST)dsclinicaltrial@daiichisankyo.co.jp

Locations

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Overlook Medical Center

Recruiting

Summit, New Jersey, United States, 07901

More Information

Sponsor

Daiichi Sankyo

Last update posted

Jun 12, 2026

Last verified

Jun, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Daiichi Sankyo on 2026-06-12.