Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab deruxtecan (DS-8201a); Capecitabine; Eribulin; Gemcitabine; Paclitaxel; Nab-paclitaxel
Intervention description: DS-8201a is a lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously; Administered according to label, as one option for Physician's Choice (determined before randomization); Administered according to label, as one option for Physician's Choice (determined before randomization); Administered according to label, as one option for Physician's Choice (determined before randomization); Administered according to label, as one option for Physician's Choice (determined before randomization); Administered according to label, as one option for Physician's Choice (determined before randomization)
Intervention MeSH terms: Paclitaxel; Camptothecin; Albumin-Bound Paclitaxel; Gemcitabine; Capecitabine; Trastuzumab; Trastuzumab deruxtecan; Immunoconjugates
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel model, randomized at a 2:1 ratio
Masking: None (Open Label)
Enrollment: 557.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Anti-HER2-Antibody Drug Conjugate (ADC); Unresectable or Metastatic; Human epidermal growth factor receptor 2 (HER2)-low; DESTINY - Breast 04

Summary:

      This study will compare DS-8201a to physician choice standard treatment.

      Participants must have HER2-low breast cancer that has been treated before.

      Participants' cancer:

        -  Cannot be removed by an operation

        -  Has spread to other parts of the body
    

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 low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)

               3. Is HR-positive or HR-negative

               4. Has progressed on, and would no longer benefit from, endocrine therapy

               5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the
                  recurrent or metastatic setting

               6. Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing
                  (per American Society of Clinical Oncology-College of American Pathologists
                  [ASCO-CAP] guidelines)

          -  Has documented radiologic progression (during or after most recent treatment)

          -  Has adequate archival tumor samples available or is wiling to provide fresh biopsies
             prior to randomization for:

               1. assessment of HER2 status

               2. assessment of post-treatment status

          -  Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1

          -  Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting
             functions

          -  Male and female participants of reproductive/childbearing potential, agrees to follow
             instructions for method(s) of contraception and agrees to avoid preserving ova or
             sperm for at least 4.5 months after treatment (or longer, per locally approved labels)

        Exclusion Criteria:

          -  Is ineligible for all options in the physician's choice arm

          -  Has breast cancer ever assessed with high-HER2 expression

          -  Has previously been treated with any anti-HER2 therapy, including an antibody drug
             conjugate

          -  Has uncontrolled or significant cardiovascular disease

          -  Has spinal cord compression or clinically active central nervous system metastases

          -  Has history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that
             required steroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis that
             cannot be ruled out by imaging at screening

          -  Has any medical history or condition that per protocol or in the opinion of the
             investigator is inappropriate for the study