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

Browse trials for

• Breast Neoplasms 12,544

Keywords

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

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's planned enrollment of 250 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Lead sponsor

Daiichi Sankyo is the lead sponsor of 316 studies on the registry; 35 are open to participants now.

Of its 51 completed or terminated interventional studies of FDA-regulated products, 38 (75%) have results posted.

Study 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.

  Drug: Trastuzumab Deruxtecan

• 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.

  Drug: Trastuzumab Deruxtecan

• 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.

  Drug: Trastuzumab Deruxtecan

• 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.

  Drug: Trastuzumab Deruxtecan

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

  Also known as: T-DXd, DS-8201a (trastuzumab derextecan), Enhertu®

Primary outcomes

1. Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT)

   TTNT is defined as the time interval from the date of first dose of T-DXd to the initiation of the next anticancer treatment or death due to any cause.

   Time frame: Until subsequent therapy or death, assessed up to 24 months

Secondary outcomes

1. Real-World Progression Free Survival (PFS)

   Real-world PFS is defined as time from date of first dose of T-DXd to time of disease progression per investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause.

   Time frame: Until progression or death, assessed up to 24 months

2. Time From Start of T-DXd to Discontinuation of T-DXd or Death (TTD)

   TTD is defined as the time interval from the date of first dose of T-DXd to the date of discontinuation of T-DXd or death due to any cause.

   Time frame: Until treatment discontinuation or death, up to 24 months

3. Objective Response Rate (ORR)

   ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to the investigator and per RECIST version 1.1 criteria.

   Time frame: Until progression, assessed up to 24 months

4. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

   TEAEs are graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. A TEAE is defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after initiating the study drug until 47 days after the last dose of the study drug.

   Time frame: Up to follow up period, up to 24 months

5. Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-C30 Score

   Change from baseline in the EORTC-QLQ-C30 scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

   Time frame: Assessed up to 24 months

6. Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-BR45 Score

   Change from baseline in the EORTC QLQ-BR45 scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

   Time frame: Assessed up to 24 months

7. Time to First and Definitive Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ) Scales

   Time to first and definitive deterioration in EORTC-QLQ scales. Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

   Time frame: Assessed up to 24 months

8. Mean Change from Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L)

   Change from baseline in EQ-5D-5L. The EQ-5D-5L is a health-related QoL questionnaire based on five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension contains five levels: no problems, slight, moderate, severe, and extreme problems. The EQ-5D-5L results can be converted into a single utility value. Utility values range from 0 to 1, with 1 corresponding to perfect health and 0 corresponding to a health status equivalent to death. In addition, participants can provide an overall rating of their current health status using a visual analog scale ranging from 0 (worse) to 100 (better).

   Time frame: Assessed up to 24 months

9. Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Index Score

   Change from baseline in EQ-5D-5L index score. The EQ-5D-5L index score ranges from less than 0 (worse) to 1 (better), with higher scores representing a better health status.

   Time frame: Assessed up to 24 months

10. Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)

    Change from baseline in EQ-5D-5L VAS. The EQ-5D-5L VAS ranging from 0 (worse) to 100 (better) is used to assess an overall rating of participant's current health status. Higher scores indicate better clinical outcomes.

    Time frame: Assessed up to 24 months

11. Time to First and Definitive Deterioration in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)

    Time to first and definitive deterioration in EQ-5D-5L VAS. The EQ-5D-5L VAS ranging from 0 (worse) to 100 (better) is used to assess an overall rating of participant's current health status. Higher scores indicate better clinical outcomes.

    Time frame: Assessed up to 24 months

12. Patient's Global Impression of Change (PGI-C) Response

    The PGI-C is a single-item questionnaire asking for the participant's overall impression of changes in clinical condition from baseline (prior to study drug initiation), where 1 is "Normal" and 7 is "Severely ill". Lower scores indicate better clinical outcome.

    Time frame: Assessed up to 24 months

13. Patient's Global Impression of Severity (PGI-S) Response

    The PGI-S is a single-item questionnaire asking for the subject's overall impression of symptoms assessed over the past week, where 1 is "Normal" and 4 is "Severe". Lower scores indicate better clinical outcome.

    Time frame: Assessed up to 24 months

14. Patient's Global Impression of Treatment Tolerability (PGI-TT) Response

    The PGI-TT is a single-item questionnaire asking for the subject's overall impression of treatment tolerability over the past week, where 1 is "Not at all" and 5 is "Very much". Higher scores indicate a worse outcome.

    Time frame: Assessed up to 24 months

Publications

• Yaziji H, Hornick JL, Troxell ML. The Suitability of Repurposed, Legacy HER2 Immunohistochemistry Assays for the Detection of HER2 Low and Ultralow Expression: Current Limitations and Potential Considerations. Appl Immunohistochem Mol Morphol. 2026 Jan 1;34(1):1-4. doi: 10.1097/PAI.0000000000001296. Epub 2025 Dec 4. No abstract available. PubMed 41342740 ↗

Individual participant data

Plan to share: Yes — De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Supporting information: Study protocol, Sap, Icf