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A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05)

NCT04622319

Description:

Patients with HER2-positive primary breast cancer (BC) who do not achieve complete response after appropriate neoadjuvant therapy are at higher risk of disease recurrence. More effective treatment options are needed for this patient population. This study will examine the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with trastuzumab emtansine (T-DM1) in high-risk patients with residual invasive breast cancer following neoadjuvant therapy.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05)
  • Official Title: A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in Participants With High-Risk HER2-Positive Primary Breast Cancer Who Have Residual Invasive Disease in Breast or Axillary Lymph Nodes Following Neoadjuvant Therapy (DESTINY-Breast05)

Clinical Trial IDs

  • ORG STUDY ID: DS8201-A-U305
  • SECONDARY ID: 2020-003982-20
  • SECONDARY ID: DESTINY-Breast05
  • SECONDARY ID: NSABP B-60
  • SECONDARY ID: GBG-103
  • SECONDARY ID: SOLTI-2001
  • NCT ID: NCT04622319

Conditions

  • HER2-Positive Primary Breast Cancer
  • Residual Invasive Breast Cancer

Interventions

DrugSynonymsArms
DS-8201aTrastuzumab deruxtecan (T-DXd)Trastuzumab deruxtecan (T-DXd)
T-DM1Trastuzumab emtansine (T-DM1)Trastuzumab ematansine (T-DM1)

Purpose

Patients with HER2-positive primary breast cancer (BC) who do not achieve complete response after appropriate neoadjuvant therapy are at higher risk of disease recurrence. More effective treatment options are needed for this patient population. This study will examine the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with trastuzumab emtansine (T-DM1) in high-risk patients with residual invasive breast cancer following neoadjuvant therapy.

Detailed Description

      This study will examine trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1)
      in patients with HER2-positive primary BC who have residual invasive disease in breast or
      axillary lymph nodes with higher risk of recurrence, which includes patients who were
      inoperable at disease presentation or had pathological node-positive status after neoadjuvant
      therapy.

      The primary objective is to compare invasive disease-free survival (IDFS) between T-DXd and
      T-DM1 treatment arms in this population. The key secondary objective of the study is to
      evaluate disease-free survival (DFS).
    

Trial Arms

NameTypeDescriptionInterventions
Trastuzumab deruxtecan (T-DXd)ExperimentalParticipants who will be randomized to receive trastuzumab deruxtecan (T-DXd) at a starting dose of 5.4 mg/kg.
  • DS-8201a
Trastuzumab ematansine (T-DM1)Active ComparatorParticipants who will be randomized to receive trastuzumab ematansine (T-DM1) at a starting dose of 3.6 mg/kg.
  • T-DM1

Eligibility Criteria

        Key Inclusion Criteria:

          -  Adults ≥18 years old (local regulatory requirements will apply if the legal age of
             consent for study participation is >18 years old)

          -  Pathologically documented HER2-positive breast cancer (BC):

               -  HER2-positive expression defined as an immunohistochemistry (IHC) score of 3+
                  and/or positive by in situ hybridization (ISH) confirmed prior to study
                  randomization

          -  Histologically confirmed invasive breast carcinoma

          -  Clinical stage at disease presentation: T1-4, N0-3, M0; patients presenting with T1N0
             tumors are not eligible

          -  Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph
             nodes following completion of neoadjuvant therapy meeting one of the following
             high-risk criteria:

               -  Inoperable breast cancer at presentation (prior to neoadjuvant therapy), defined
                  as clinical stages T4, N0-3, M0 or T1-3, N2-3, M0

               -  Operable at presentation, defined as clinical stages T1-3,N0-1,M0, with axillary
                  node positive disease (ypN1-3) following neoadjuvant therapy

          -  Completion of neoadjuvant systemic chemotherapy, including taxane and HER2-directed
             treatment prior to surgery

               -  Systemic therapy must consist of at least 6 cycles of chemotherapy with a total
                  duration of at least 16 weeks, including at least 9 weeks of trastuzumabpertuzumab) and at least 9 weeks of taxane based chemotherapy. Patients may have
                  received an anthracycline as part of neoadjuvant therapy in addition to taxane
                  chemotherapy.

          -  Adequate excision as confirmed per medical records: surgical removal of all clinically
             evident disease in the breast and lymph nodes.

          -  An interval of no more than 12 weeks between the date of last surgery and the date of
             randomization.

          -  Known hormone receptor (HR) status, per local laboratory assessment, as defined by
             ASCO-CAP guidelines (≥1%): HR positive status defined by either positive estrogen
             receptor (ER) and/or positive progesterone receptor (PR) status. HR-negative status
             defined by both known negative ER and known negative PR.

          -  Left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to randomization.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening.

          -  Has adequate organ function within 14 days before randomization.

        Key Exclusion Criteria:

          -  Stage IV (metastatic) BC

          -  History of any prior (ipsi- or contralateral) breast cancer except lobular carcinoma
             in situ (LCIS)

          -  Evidence of clinically evident gross residual or recurrent disease following
             neoadjuvant therapy and surgery

          -  Prior treatment with T-DXd, T-DM1 or other anti-HER2 antibody-drug conjugate (ADC)

          -  History of exposure to the following cumulative doses of anthracyclines:

               -  Doxorubicin > 240 mg/m^2

               -  Epirubicin or Liposomal Doxorubicin-Hydrochloride > 480 mg/m^2

               -  For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m^2

          -  History of other malignancy within the last 5 years except for appropriately treated
             CIS of the cervix, nonmelanoma skin carcinoma, Stage I melanoma skin carcinoma, Stage
             I uterine cancer, or other appropriately treated non-breast malignancies

          -  History of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required
             steroids and/or has ILD/pneumonitis noted on computed tomography (CT) scan of the
             chest at Screening (asymptomatic interstitial changes confined to recent radiation
             therapy fields are not excluded)

          -  Known pulmonary compromise resulting from intercurrent pulmonary illnesses including,
             but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within
             three months prior to randomization, severe asthma, severe chronic obstructive
             pulmonary disease [COPD], restrictive lung disease).

          -  Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement
             (eg, Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior lobectomy or
             pneumonectomy

          -  Medical history of myocardial infarction (MI) within 6 months before randomization,
             symptomatic congestive heart failure (CHF) (New York Heart Association Class II to
             IV), troponin levels consistent with MI as defined according to the manufacturer 28
             days prior to randomization
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Invasive Disease-free Survival (IDFS) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
Time Frame:Randomization to date of invasive local, axillary or distant recurrence, invasive contralateral breast cancer or death from any cause (whichever occurs first), up to approximately 81 months postdose
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease-free Survival (DFS) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
Time Frame:Randomization to date of the first occurrence of an IDFS event including second primary non-breast cancer event or contralateral or ipsilateral ductal carcinoma in situ (whichever occurs first), up to approximately 81 months postdose
Safety Issue:
Description:
Measure:Overall Survival (OS) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
Time Frame:Randomization to date of death from any cause, up to approximately 81 months postdose
Safety Issue:
Description:
Measure:Distant Recurrence-free Interval (DRFI) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
Time Frame:Randomization to date of distant recurrence, up to approximately 81 months postdose
Safety Issue:
Description:
Measure:Brain Metastases-free Interval (BMFI) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
Time Frame:Randomization to date of brain metastasis, up to approximately 81 months postdose
Safety Issue:
Description:
Measure:Percentage of Treatment-emergent Adverse Events in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment
Time Frame:Baseline up to approximately 81 months postdose
Safety Issue:
Description:
Measure:Serum Concentrations of Trastuzumab Deruxtecan (T-DXd), total anti-HER2 antibody, and Active Metabolite MAAA-1181a
Time Frame:Pre-dose on Day 1 of Cycles 1, 4 and 10 and within 15 minutes post-dose on Day 1 of Cycles 1 and 4 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd)
Time Frame:Baseline up to approximately 81 months postdose
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • HER2-Positive Primary Breast Cancer
  • Residual Invasive Breast Cancer
  • Trastuzumab Deruxtecan
  • Trastuzumab Emtansine

Last Updated

July 9, 2021