Breast Cancer
Conditions
Keywords
Breast Cancer, Metastatic breast cancer, DS 8201a, DESTINY - Breast 02
Brief summary
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
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.
Interventions
DRUGTrastuzumab deruxtecan
DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as intravenous (IV) dose
DRUGCapecitabine
Investigator's choice Standard of Care when combined with trastuzumab or lapatinib
DRUGLapatinib
Investigator's choice Standard of Care when combined with capecitabine
DRUGTrastuzumab
Investigator's choice Standard of Care when combined with capecitabine
Sponsors
Daiichi Sankyo
Daiichi Sankyo Co., Ltd.
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline up to 46 months postdose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | Baseline up to 46 months postdose | 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. |
| 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 | Baseline up to 46 months postdose | 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. |
| Duration of Response (DoR) Based on BICR in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | Baseline up to 46 months postdose | 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. |
| 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 | Up to 46 months | 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. |
Countries
Australia, Belgium, Brazil, Czechia, France, Germany, Greece, Israel, Italy, Japan, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORGlobal Team Leader
Daiichi Sankyo
Participant flow
Recruitment details
A total of 608 participants were enrolled at study sites in 15 countries. Primary results reported is from first participant randomized up to data cut-off date of 30 Jun 2022. The results presented are based on primary analysis up to 46 months.
Pre-assignment details
Participants in The Physician's Choice (TPC) group were randomized to 1 of the following 2 regimens: trastuzumab/capecitabine or lapatinib/capecitabine. As prespecified in the protocol, participants were assessed and reported separately per comparator arm for the disposition, baseline characteristics, and safety tables. For efficacy assessments, all participants in the TPC group were combined and assessed together.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Deruxtecan (T-DXd) Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W). | 406 |
| Trastuzumab+Capecitabine Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Trastuzumab/Capecitabine. | 91 |
| Lapatinib+Capecitabine Participants with HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), who received investigator's choice treatment, Lapatinib/Capecitabine. | 111 |
| Total | 608 |
Baseline characteristics
| Characteristic | Trastuzumab+Capecitabine | Lapatinib+Capecitabine | Total | Trastuzumab Deruxtecan (T-DXd) |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 20 Participants | 123 Participants | 85 Participants |
| Age, Categorical Between 18 and 65 years | 73 Participants | 91 Participants | 485 Participants | 321 Participants |
| Age, Continuous | 55.7 years STANDARD_DEVIATION 11.4 | 54.6 years STANDARD_DEVIATION 11.06 | 54.8 years STANDARD_DEVIATION 11.73 | 54.6 years STANDARD_DEVIATION 11.99 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 36 Participants | 178 Participants | 122 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 17 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 26 Participants | 15 Participants |
| Race (NIH/OMB) White | 66 Participants | 61 Participants | 384 Participants | 257 Participants |
| Region of Enrollment Australia | 7 participants | 4 participants | 21 participants | 10 participants |
| Region of Enrollment Belgium | 1 participants | 0 participants | 5 participants | 4 participants |
| Region of Enrollment Brazil | 10 participants | 8 participants | 59 participants | 41 participants |
| Region of Enrollment Czechia | 2 participants | 0 participants | 3 participants | 1 participants |
| Region of Enrollment France | 8 participants | 12 participants | 57 participants | 37 participants |
| Region of Enrollment Germany | 2 participants | 5 participants | 19 participants | 12 participants |
| Region of Enrollment Greece | 3 participants | 2 participants | 14 participants | 9 participants |
| Region of Enrollment Israel | 0 participants | 4 participants | 18 participants | 14 participants |
| Region of Enrollment Italy | 3 participants | 17 participants | 53 participants | 33 participants |
| Region of Enrollment Japan | 6 participants | 18 participants | 70 participants | 46 participants |
| Region of Enrollment South Korea | 11 participants | 17 participants | 94 participants | 66 participants |
| Region of Enrollment Spain | 8 participants | 7 participants | 44 participants | 29 participants |
| Region of Enrollment Turkey | 12 participants | 4 participants | 52 participants | 36 participants |
| Region of Enrollment United Kingdom | 4 participants | 4 participants | 35 participants | 27 participants |
| Region of Enrollment United States | 14 participants | 9 participants | 64 participants | 41 participants |
| Sex: Female, Male Female | 89 Participants | 111 Participants | 603 Participants | 403 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 143 / 406 | 40 / 91 | 46 / 111 |
| other Total, other adverse events | 398 / 404 | 79 / 87 | 102 / 108 |
| serious Total, serious adverse events | 103 / 404 | 19 / 87 | 27 / 108 |
Outcome results
Primary
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.
Time frame: Baseline up to 46 months postdose
Population: Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 30 Jun 2022.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | 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 | 17.8 months |
| Treatment of Investigator's/Physician's Choice (TPC) | 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 | 6.9 months |
p-value: <0.00000195% CI: [0.284, 0.4535]Log Rank
Secondary
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.
Time frame: Baseline up to 46 months postdose
Population: Duration of Response (DoR) was assessed in the Full Analysis Set of participants with confirmed CR/PR at data cut-off date of 30 Jun 2022.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Duration of Response (DoR) Based on BICR in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | 19.6 months |
| Treatment of Investigator's/Physician's Choice (TPC) | Duration of Response (DoR) Based on BICR in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | 8.3 months |
Secondary
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.
Time frame: Baseline up to 46 months postdose
Population: Overall survival (OS) was assessed in the Full Analysis Set at data cut-off date of 30 Jun 2022.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Overall Survival (OS) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | 39.2 months |
| Treatment of Investigator's/Physician's Choice (TPC) | Overall Survival (OS) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine | 26.5 months |
p-value: 0.002195% CI: [0.5023, 0.8605]Log Rank
Secondary
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.
Time frame: Baseline up to 46 months postdose
Population: Objective response rate (ORR) was assessed in the Full Analysis Set at data cut-off date of 30 Jun 2022.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | 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 | BICR | 69.7 Percentage of Participants |
| Trastuzumab Deruxtecan (T-DXd) | 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 | Investigator Assessment | 74.1 Percentage of Participants |
| Treatment of Investigator's/Physician's Choice (TPC) | 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 | BICR | 29.2 Percentage of Participants |
| Treatment of Investigator's/Physician's Choice (TPC) | 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 | Investigator Assessment | 26.7 Percentage of Participants |
Comparison: Statistical Analysis for BICR Assessmentp-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Statistical Analysis for Investigator Assessmentp-value: <0.0001Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Up to 46 months
Population: Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 30 Jun 2022.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | 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 | 16.7 months |
| Treatment of Investigator's/Physician's Choice (TPC) | 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 | 5.5 months |
p-value: <0.00000195% CI: [0.227, 0.3524]Log Rank