Clinical Trials /

Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer

NCT04494425

Description:

This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer
  • Official Title: A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy in the Metastatic Setting (DESTINY-Breast06)

Clinical Trial IDs

  • ORG STUDY ID: D9670C00001
  • NCT ID: NCT04494425

Conditions

  • Advanced or Metastatic Breast Cancer

Interventions

DrugSynonymsArms
Trastuzumab deruxtecanDS-8201a; T-DXdTrastuzumab deruxtecan
CapecitabineStandard of Care
PaclitaxelStandard of Care
Nab-PaclitaxelStandard of Care

Purpose

This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.

Detailed Description

      Eligible patients will be those patients who have had disease progression on at least 2
      previous lines of endocrine therapies given for the treatment of metastatic disease. All
      patients must have historically confirmed HR positive (either estrogen receptor and/or
      progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC >0
      <1+ expression, as determined by central laboratory testing results, advanced or metastatic
      breast cancer.

      The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan
      compared with investigator's choice chemotherapy. This study aims to see if trastuzumab
      deruxtecan allows patients to live longer without the cancer getting worse, or simply to live
      longer, compared to patients receiving standard of care chemotherapy. This study is also
      looking to see how the treatment and the cancer affects patients' quality of life.
    

Trial Arms

NameTypeDescriptionInterventions
Trastuzumab deruxtecanExperimentalTrastuzumab deruxtecan (T-DXd; DS-8201a) arm
  • Trastuzumab deruxtecan
Standard of CareActive ComparatorInvestigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
  • Capecitabine
  • Paclitaxel
  • Nab-Paclitaxel

Eligibility Criteria

        Key Inclusion Criteria:

          -  Patients must be ≥18 years of age

          -  Pathologically documented breast cancer that:

               1. is advanced or metastatic

               2. has a history of HER2-low or negative expression defined as IHC 2+/ISH- or IHC 1+
                  (ISH- or untested) or HER2 IHC 0 (ISH- or untested)

               3. has HER2-low or HER2 IHC >0 <1+ expression

               4. was never previously HER2-positive

               5. is documented HR+ disease in the metastatic setting.

          -  No prior chemotherapy for advanced or metastatic breast cancer.

          -  Has adequate tumor samples for assessment of HER2 status

          -  Either disease progression on at least 2 previous lines of endocrine therapy with or
             without a targeted therapy in the metastatic setting or disease progression within 24
             months of starting adjuvant endocrine therapy and on at least 1 previous line of
             endocrine therapy in the metastatic setting

          -  Has protocol-defined adequate organ and bone marrow function

        Key Exclusion Criteria:

          -  Ineligible for all options in the investigator's choice chemotherapy arm

          -  Lung-specific intercurrent clinically significant illnesses

          -  Uncontrolled or significant cardiovascular disease or infection

          -  Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected
             ILD/pneumonitis that cannot be ruled out by imaging at screening

          -  Patients with spinal cord compression or clinically active central nervous system
             metastases

          -  Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless
             of treatment arm assignment
      
Maximum Eligible Age:105 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) - in HR+, HER2-low populaton
Time Frame:Until progression or death, assessed up to approximately 60 months
Safety Issue:
Description:Defined as time from date of randomization until the date of objective radiological disease progression by blinded independent central review (BICR) assessment according to RECIST 1.1 or death.

Secondary Outcome Measures

Measure:Overall Survival (OS) - in HR+, HER2-low population
Time Frame:Until death, assessed up to approximately 60 months
Safety Issue:
Description:Defined as the time from randomization to death due to any cause
Measure:Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2-Low and HER2 IHC >0<1+)
Time Frame:Until progression or death, assessed up to approximately 60 months
Safety Issue:
Description:PFS by BICR according to RECIST 1.1 in ITT population
Measure:Overall Survival - in intent to treat (ITT) population (HER2-Low and HER2 IHC >0<1+)
Time Frame:Until death, assessed up to approximately 60 months
Safety Issue:
Description:OS in the ITT population
Measure:Objective Response Rate (ORR) in HR+, HER-2 low populaton
Time Frame:Until progression, assessed up to approximately 60 months
Safety Issue:
Description:ORR defined as the percentage of patients with at least one visit response of complete or partial response (CR or PR) by BICR and Investigator assessment according to RECIST 1.1.
Measure:Duration of response (DoR) - in HR+, HER-2 low populaton
Time Frame:Until progression, assessed up to approximately 60 months
Safety Issue:
Description:DoR defined as the time from the date of first documented response (CR/PR) until the first progression or death in the absence of disease progression by BICR and Investigator assessment according to RECIST 1.1
Measure:Progression Free Survival by Investigator assessment - in the HR+, HER2-low population
Time Frame:Until progression or death, assessed up to approximately 60 months
Safety Issue:
Description:PFS using investigator assessments according to RECIST 1.1 in the HER2-low population
Measure:Objective Response Rate (ORR) in the ITT population
Time Frame:Until progression, assessed up to approximately 60 months
Safety Issue:
Description:ORR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
Measure:Duration of response (DoR) - in the ITT population
Time Frame:Until progression, assessed up to approximately 60 months
Safety Issue:
Description:DoR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
Measure:PFS2 by Investigator assessment, time to first subsequent therapy (TFST) and time to second subsequent treatment or death (TSST) - in HR+, HER2-low and the ITT population
Time Frame:Assessed up to approximately 60 months
Safety Issue:
Description:PFS2 defined as time from randomisation to second progression or death. TFST defined as a time elapsed from randomization to first subsequent therapy or death. TSST defined as a time elapsed from randomization to second subsequent therapy or death.
Measure:Safety and tolerability of drugs; number of adverse events (AEs)
Time Frame:Up to follow-up period, approximately 60 months
Safety Issue:
Description:Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm
Measure:Serum concentration of trastuzumab deruxtecan
Time Frame:Up to Cycle 8, approximately Week 24; each cycle is 21 days
Safety Issue:
Description:Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
Measure:Health-related quality of life - EORTC-QLQ-C30
Time Frame:Assessed up to approximately 60 months
Safety Issue:
Description:Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30
Measure:Immunogenicity of trastuzumab deruxtecan
Time Frame:Up to follow-up period, approximately 60 months
Safety Issue:
Description:Percentage of patients who develop ADA for trastuzumab deruxtecan
Measure:Time to deterioration in EORTC-QLQ-C30 scores
Time Frame:Assessed up to approximately 60 months
Safety Issue:
Description:Time to deterioration from baseline in EORTC-QLQ-C30 scores
Measure:Health-related quality of life - EORTC-QLQ-C45
Time Frame:Assessed up to approximately 60 months
Safety Issue:
Description:Change from baseline in the physical functioning subscale of the EORTC-QLQ-C45

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Breast Cancer
  • HR positive
  • HER2-Low
  • HER2-Negative
  • Trastuzumab Deruxtecan (T-DXd; DS-8201a)
  • Anti-HER2-Antibody Drug Conjugate (ADC)
  • DESTINY-Breast06

Last Updated

July 28, 2020