This study will compare DS 8201a to standard treatment.

Participants must have HER2 breast cancer that has been treated before.

Their cancer:

• cannot be removed by an operation
• has spread to other parts of the body

The study is designed to compare DS 8201a versus standard of care (investigator's choice) in subjects with unresectable and/or metastatic breast cancer previously treated with T-DM1.

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 ado-trastuzumab emtansine (T-DM1)

• 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.

• Male and female participants of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least:

  1. 7 months after the last dose of DS-8201a (females); 4.5 months after last dose of DS-8201a (males)
  2. 6 months after the last dose of lapatinib/capecitabine for female participants (3 months for male participants)
  3. 7 months after the last dose of trastuzumab/capecitabine

• Has adequate hematopoietic, renal and hepatic functions

Exclusion Criteria:

• Has previously participated in an antibody drug conjugate study sponsored by Daiichi Sankyo. 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 had prior treatment with capecitabine
• Has uncontrolled or significant cardiovascular disease
• Has a 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 active central nervous system (CNS) metastases

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.

Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.