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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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A Phase 3, Multicenter, Randomized, Open-label, Active-controlled Study of Trastuzumab Deruxtecan (DS-8201a), an Anti-HER2-antibody Drug Conjugate, Versus Treatment of Investigator's Choice for HER2-positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab deruxtecan
* Drug: Capecitabine
* Drug: Lapatinib
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is the age of majority in their country Has pathologically documented breast cancer that: is unresectable or metastatic has confirmed HER2-positive expression as determined according to American Society of Clinical Oncology - College of American Pathologists guidelines evaluated at a central laboratory 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: 7 months after the last dose of DS-8201a (females); 4.5 months after last dose of DS-8201a (males) 6 months after the last dose of lapatinib/capecitabine for female participants (3 months for male participants) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab deruxtecan (DS-8201a)<br>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 | Drug: Trastuzumab deruxtecan<br>* DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as intravenous (IV) dose<br>* Other names: T-DXd;|
| Active Comparator: Trastuzumab+capecitabine<br>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 | Drug: Capecitabine<br>* Investigator's choice Standard of Care when combined with trastuzumab or lapatinib<br>* Other names: Investigator's Choice Comparative Therapy;Drug: Trastuzumab<br>* Investigator's choice Standard of Care when combined with capecitabine<br>* Other names: Investigator's Choice Comparative Therapy;|
| Active Comparator: Lapatinib+capecitabine<br>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 | Drug: Capecitabine<br>* Investigator's choice Standard of Care when combined with trastuzumab or lapatinib<br>* Other names: Investigator's Choice Comparative Therapy;Drug: Lapatinib<br>* Investigator's choice Standard of Care when combined with capecitabine<br>* Other names: Investigator's Choice Comparative Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | Progression-free survival (PFS) by BICR was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. | Baseline up to 46 months postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there is no death reported for a subject before the data cutoff for OS analysis, OS will be censored at the last contact date at which the subject is known to be alive. | Baseline up to 46 months postdose | 
| Percentage of Participants With Objective Response Rate (ORR) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR and investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on BICR and Investigator Assessment is reported. | Baseline up to 46 months postdose | 
| Duration of Response (DoR) Based on BICR in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR in participants with confirmed CR/PR based on BICR and investigator assessment is reported. | Baseline up to 46 months postdose | 
| Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | Progression-free survival (PFS) by investigator assessment was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. | Up to 46 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Metastatic breast cancer, DS 8201a, DESTINY - Breast 02