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

PHASE3RECRUITING

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.

Study details:

The primary endpoint of interest in this study is time to next treatment (TTNT), a measure that will determine how long T-DXd allows patients to derive clinical benefit from the study drug.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Sign and date the main informed consent form
  2. Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion.
  3. Pathologically documented Breast Cancer (BC) tumor
  4. Is unresectable and/or metastatic.
  5. Is hormone receptor-negative or hormone receptor-positive.
  6. Must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative.
  7. Has confirmed HER2 IHC 1+ or IHC 2+/ISH- (HER2-low) status or HER2 IHC 0 status as determined according to ASCO CAP 2018 guidelines based on sample collected during Tissue Screening as described above.
  8. Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per ASCO CAP guidelines).
  9. Was never previously treated with anti-HER2 therapy in the metastatic setting.
  10. Has had at least one and up to two prior lines of therapy in the metastatic setting.
  11. 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
  12. Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging.
  13. 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.
  14. Has an Eastern Cooperative Oncology Group performance status of 0 or 1.
  15. Has a minimum life expectancy of 12 weeks at Screening.
  16. Has a left ventricular ejection fraction ≥50% within 28 days before enrollment.
  17. Has adequate organ and bone marrow function within 28 days before enrollment.
  18. Has adequate treatment washout period before enrollment.
  19. Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception.

Exclusion criteria

  1. Prior treatment with an antibody drug conjugate (ADC).
  2. Uncontrolled or significant cardiovascular disease.
  3. Has a corrected QT interval prolongation.
  4. 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.
  5. Has spinal cord compression or clinically active central nervous system metastases.
  6. 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.
  7. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
  8. Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
  9. Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
  10. Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
  11. 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.
  12. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline.
  13. Is pregnant or breastfeeding or planning to become pregnant.
  14. Lung-specific intercurrent clinically significant illnesses.
  15. Any autoimmune, connective tissue, or inflammatory disorders.
  16. Prior complete pneumonectomy.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE3

trial

Study ID

NCT05950945

Intervention or treatment

DRUG: Trastuzumab Deruxtecan

Conditions

  • Breast Cancer

  • Condition: Breast Cancer

  • DRUG: Trastuzumab Deruxtecan

  • North Sydney, New South Wales, Australia and more

  • Sponsor: Daiichi Sankyo

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Mater Hospital Sydney

Select from list below to view details:

  • Mater Hospital Sydney

    North Sydney, New South Wales, Australia

  • Monash Medical Centre Moorabbin

    East Bentleigh, Victoria, Australia

  • Fiona Stanley Hospital

    Murdoch, Australia

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Who is running the clinical trial?

DS

Daiichi Sankyo

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
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

          What is the study measuring?

          Primary Outcome

          MeasureDescriptionTime Frame
          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.Until subsequent therapy or death, assessed up to 24 months

          Secondary Outcome

          MeasureDescriptionTime Frame
          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.Until progression or death, assessed up to 24 months
          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.Until treatment discontinuation or death, up to 24 months
          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.Until progression, assessed up to 24 months
          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.Up to follow up period, up to 24 months
          Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-C30 ScoreChange 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.Assessed up to 24 months
          Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-BR45 ScoreChange 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.Assessed up to 24 months
          Time to First and Definitive Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ) ScalesTime 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.Assessed up to 24 months
          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).Assessed up to 24 months
          Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Index ScoreChange 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.Assessed up to 24 months
          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.Assessed up to 24 months
          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.Assessed up to 24 months
          Patient's Global Impression of Change (PGI-C) ResponseThe 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.Assessed up to 24 months
          Patient's Global Impression of Severity (PGI-S) ResponseThe 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.Assessed up to 24 months
          Patient's Global Impression of Treatment Tolerability (PGI-TT) ResponseThe 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.Assessed up to 24 months
          Are you running this trial?If you're a clinic or sponsor, you can claim this study.
          Claim this trial

          References

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

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