DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03]
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab deruxtecan (T-DXd); Ado-trastuzumab emtansine (T-DM1)
Intervention description: T-DXd is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously.; The treatment will be in accordance with the approved label.
Intervention MeSH terms: Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine; Trastuzumab deruxtecan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 524.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer; Metastatic breast cancer; DS-8201a; DESTINY - Breast 03

Summary:

      This study is designed to compare the anti-tumor activity as well as the safety and efficacy
      of DS-8201a versus T-DM1 in HER2-positive, unresectable and/or metastatic breast cancer
      subjects previously treated with trastuzumab and taxane.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is the age of majority in their country

          -  Has pathologically documented breast cancer that:

               1. is unresectable or metastatic

               2. has confirmed HER2-positive expression as determined according to American
                  Society of Clinical Oncology - College of American Pathologists guidelines
                  evaluated at a central laboratory

               3. was previously treated with trastuzumab and taxane in the advanced/metastatic
                  setting or progressed within 6 months after neoadjuvant or adjuvant treatment
                  involving a regimen including trastuzumab and taxane

          -  Has documented radiologic progression (during or after most recent treatment or within
             6 months after completing adjuvant therapy)

          -  Is HER2 positive as confirmed by central laboratory assessment of most recent tumor
             tissue sample available. If archived tissue is not available, agrees to provide a
             fresh biopsy.

          -  If of reproductive/childbearing potential, agrees to use a highly effective form of
             contraception or avoid intercourse during and upon completion of the study for 7
             months after the last dose of DS-8201a (females); 4.5 months after last dose of
             DS-8201a (males) or 7 months after the last dose of T-DM1

          -  Has adequate renal and hepatic function

        Exclusion Criteria:

          -  Has previously been treated with an anti-HER2 antibody drug conjugate (ADC) in the
             metastatic setting. Prior treatment in the adjuvant/neo-adjuvant setting would be
             allowed if progression of disease did not occur within 12 months of end of adjuvant
             therapy

          -  Has uncontrolled or significant cardiovascular disease

          -  Has a history of (noninfectious) 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 (CNS)
             metastases, defined as untreated and symptomatic, or requiring therapy with
             corticosteroids or anticonvulsants to control associated symptoms.

               1. Participants with clinically inactive brain metastases may be included in the
                  study.

               2. Participants with treated brain metastases that are no longer symptomatic and who
                  require no treatment with corticosteroids or anticonvulsants may be included in
                  the study if they have recovered from the acute toxic effect of radiotherapy. A
                  minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy
                  and study enrollment.