for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
completion around



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

Official Title

A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects


This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer participants.

The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.


Breast Cancer, Anti-HER2-Antibody Drug Conjugate (ADC), Unresectable or Metastatic, Human epidermal growth factor receptor 2 (HER2)-low, DESTINY - Breast 04, Breast Neoplasms, Paclitaxel, Camptothecin, Albumin-Bound Paclitaxel, Gemcitabine, Capecitabine, Trastuzumab, Trastuzumab deruxtecan, Immunoconjugates, Trastuzumab deruxtecan (DS-8201a), Eribulin, Nab-paclitaxel


You can join if…

Open to people ages 18 years and up

  • 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)

You CAN'T join if...

  • 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


  • University of California at San Francisco (PARENT)
    San Francisco California 94158 United States
  • Stanford Cancer Institute
    Palo Alto California 94305 United States


in progress, not accepting new patients
Start Date
Completion Date
Daiichi Sankyo
Phase 3 research study
Study Type
About 557 people participating
Last Updated