DS-8201a in Pre-treated HER2 Breast Cancer That Cannot be Surgically Removed or Has Spread [DESTINY-Breast02]

Daiichi Sankyo

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Trastuzumab; Drug: Trastuzumab deruxtecan; Drug: Capecitabine; Drug: Lapatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03523585

2018-000221-31 (EudraCT Number)

184017 (Registry Identifier)

DESTINY-Breast02 (Other Identifier)

DS8201-A-U301

Details and patient eligibility

About

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

Full description

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.

Enrollment: 608 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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608 participants in 3 patient groups

Trastuzumab deruxtecan (DS-8201a)

Experimental group

Description:

HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to treatment with DS-8201a

Treatment:

Drug: Trastuzumab deruxtecan

Trastuzumab+capecitabine

Active Comparator group

Description:

HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to investigator's choice treatment with Trastuzumab/capecitabine

Treatment:

Drug: Capecitabine

Drug: Trastuzumab

Lapatinib+capecitabine

Active Comparator group

Description:

HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to investigator's choice treatment with Lapatinib/capecitabine

Treatment:

Drug: Lapatinib

Drug: Capecitabine