Breast Cancer
Conditions
Keywords
HER-2 positive breast cancer, Metastatic or Unresectable, Resistant or refractory to T-DM1, DESTINY - Breast 01, Trastuzumab deruxtecan, T-DXd
Brief summary
Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond or become resistant to current treatment. DS-8201a is a new experimental product that is a combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may slow down tumor growth. This might improve outcomes for these patients.
Interventions
DRUGDS-8201a
DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.
Sponsors
AstraZeneca
Daiichi Sankyo Co., Ltd.
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
In Part 1, about 60 trastuzumab emtansine (T-DM1) resistant/refractory patients initially will be randomized into three treatment groups (low, medium and high doses) for Pharmacokinetics (PK), then about another 60 will be randomized into low and high doses to determine recommended dose (RD). After that, about 100 will receive the recommended dose in an open-label continuation stage (Part 2). About 10 TDM-1 intolerant patients will join the continuation stage as an exploratory only arm.
Intervention model description
HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women the age of majority in their country * Has pathologically documented breast cancer that: 1. is unresectable or metastatic 2. has HER2 positive expression confirmed per protocol * Has an adequate tumor sample * Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * Has protocol-defined adequate cardiac, renal and hepatic function * Agrees to follow protocol-defined method(s) of contraception
Exclusion criteria
* Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia * Has a corrected QT interval (QTc) prolongation to \> 450 millisecond (ms) in males and \> 470 ms in females * Has a medical history of clinically significant lung disease * Is suspected to have certain other protocol-defined diseases based on imaging at screening period * Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise: 1. safety or well-being of the participant or offspring 2. safety of study staff 3. analysis of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) | The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) | Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported. |
| Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) | Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease. |
| Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) | The estimated duration of confirmed response (complete response \[CR\] or partial response \[PR\]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause. |
| Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) | The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments. |
| Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline up to Week 6, 12, 18, 24, 30, 36 post dose | Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters. |
| Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Day 0 to Day 47 post last dose | TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization. |
| Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) | The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause. |
Countries
Belgium, Canada, France, Italy, Japan, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants who met all of the inclusion and none of the exclusion criteria were enrolled and randomized to treatment (Part 1) or received DS-8201a at the recommended dose (Part 2).
Pre-assignment details
In Part 1, participants were randomized 1:1:1 to either 5.4 mg/kg, 6.4 mg/kg, or 7.4 mg/kg dose of DS-8201a. Two doses randomized 1:1 (5.4 or 6.4 mg/kg) were further evaluated. In Part 2, all T-DM1 resistant refractory participants (cohort 2a) or T-DM1 intolerant (cohort 2b) received DS-8201a at the recommended dose.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: DS-8201a Low Dose T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a low dose (5.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases. | 50 |
| Part 1: DS-8201a Medium Dose T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a medium dose (6.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases. | 48 |
| Part 1: DS-8201a High Dose T-DM1 resistant/refractory (R/R) participants randomized to receive DS-8201a high dose (7.4 mg/kg) in the pharmacokinetic (PK) and dose-finding phases. | 21 |
| Part 2a: DS-8201a Low Dose All T-DM1 resistant/refractory (R/R) participants who were treated at the recommended (5.4 mg/kg) dose in Part 2a in the continuation phase. | 130 |
| Part 2b (Exploratory): DS-8201a Low Dose All participants who were previously treated with T-DM1 and were randomized to receive DS8201a low dose (5.4 mg/kg) in Part 2b in the continuation phase. | 4 |
| Total | 253 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 14 | 13 | 9 | 22 | 2 |
| Overall Study | Death | 1 | 1 | 0 | 6 | 0 |
| Overall Study | Other | 2 | 5 | 0 | 14 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 1 | 7 | 0 |
| Overall Study | Progressive Disease | 24 | 23 | 11 | 66 | 1 |
| Overall Study | Study Terminated by Sponsor | 3 | 1 | 0 | 7 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 4 | 0 | 8 | 1 |
Baseline characteristics
| Characteristic | Total | Part 1: DS-8201a Low Dose | Part 1: DS-8201a Medium Dose | Part 1: DS-8201a High Dose | Part 2a: DS-8201a Low Dose | Part 2b (Exploratory): DS-8201a Low Dose |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 64 Participants | 15 Participants | 15 Participants | 5 Participants | 29 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 189 Participants | 35 Participants | 33 Participants | 16 Participants | 101 Participants | 4 Participants |
| Age, Continuous | 55.8 years STANDARD_DEVIATION 11.8 | 57.9 years STANDARD_DEVIATION 11.3 | 55.8 years STANDARD_DEVIATION 13 | 54.4 years STANDARD_DEVIATION 10.5 | 55.4 years STANDARD_DEVIATION 11.9 | 49.8 years STANDARD_DEVIATION 9.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 104 Participants | 22 Participants | 22 Participants | 12 Participants | 47 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 132 Participants | 24 Participants | 23 Participants | 8 Participants | 76 Participants | 1 Participants |
| Region of Enrollment Belgium | 9 participants | 0 participants | 2 participants | 0 participants | 7 participants | 0 participants |
| Region of Enrollment France | 20 participants | 2 participants | 1 participants | 0 participants | 17 participants | 0 participants |
| Region of Enrollment Italy | 10 participants | 0 participants | 1 participants | 0 participants | 8 participants | 1 participants |
| Region of Enrollment Japan | 56 participants | 16 participants | 15 participants | 11 participants | 14 participants | 0 participants |
| Region of Enrollment South Korea | 40 participants | 7 participants | 7 participants | 0 participants | 25 participants | 1 participants |
| Region of Enrollment Spain | 29 participants | 10 participants | 8 participants | 0 participants | 11 participants | 0 participants |
| Region of Enrollment United Kingdom | 12 participants | 0 participants | 0 participants | 0 participants | 12 participants | 0 participants |
| Region of Enrollment United States | 77 participants | 15 participants | 14 participants | 10 participants | 36 participants | 2 participants |
| Sex: Female, Male Female | 253 Participants | 50 Participants | 48 Participants | 21 Participants | 130 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 33 / 50 | 30 / 48 | 18 / 21 | 86 / 130 | 3 / 4 |
| other Total, other adverse events | 50 / 50 | 48 / 48 | 21 / 21 | 129 / 130 | 4 / 4 |
| serious Total, serious adverse events | 14 / 50 | 11 / 48 | 8 / 21 | 42 / 130 | 1 / 4 |
Outcome results
Primary
Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.
Time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Population: Objective response rate (ORR) was assessed in the Enrolled Analysis Set.at data cut-off date of 21 March 2019
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 and Part 2a: DS-8201a Low Dose | Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | 109 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | 111 Participants |
Secondary
Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.
Time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Population: Best overall tumor response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 and Part 2a: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Progressive disease | 0 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Partial response | 34 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Non-evaluable | 1 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Stable disease | 10 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Complete response | 3 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Stable disease | 3 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Progressive disease | 0 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Non-evaluable | 0 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Partial response | 18 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Complete response | 0 Participants |
| Part 1: DS-8201a Medium Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Stable disease | 59 Participants |
| Part 1: DS-8201a Medium Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Complete response | 4 Participants |
| Part 1: DS-8201a Medium Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Partial response | 112 Participants |
| Part 1: DS-8201a Medium Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Progressive disease | 4 Participants |
| Part 1: DS-8201a Medium Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Non-evaluable | 1 Participants |
| Part 1: DS-8201a High Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Progressive disease | 4 Participants |
| Part 1: DS-8201a High Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Partial response | 112 Participants |
| Part 1: DS-8201a High Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Complete response | 6 Participants |
| Part 1: DS-8201a High Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Stable disease | 61 Participants |
| Part 1: DS-8201a High Dose | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Non-evaluable | 1 Participants |
Secondary
Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.
Time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Population: Disease control rate (DCR) and clinical benefit rate (CBR) were assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 and Part 2a: DS-8201a Low Dose | Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Disease control rate | 47 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Clinical benefit rate | 41 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Clinical benefit rate | 20 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Disease control rate | 21 Participants |
| Part 1: DS-8201a Medium Dose | Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Disease control rate | 175 Participants |
| Part 1: DS-8201a Medium Dose | Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Clinical benefit rate | 127 Participants |
| Part 1: DS-8201a High Dose | Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Disease control rate | 179 Participants |
| Part 1: DS-8201a High Dose | Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Clinical benefit rate | 130 Participants |
Secondary
Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
The estimated duration of confirmed response (complete response \[CR\] or partial response \[PR\]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.
Time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Population: Participants with CR or PR were analyzed. Estimated duration of response was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 and Part 2a: DS-8201a Low Dose | Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | NA months |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | 6.0 months |
| Part 1: DS-8201a Medium Dose | Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | NA months |
| Part 1: DS-8201a High Dose | Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | NA months |
Secondary
Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.
Time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Population: Objective response rate (ORR) was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 and Part 2a: DS-8201a Low Dose | Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | 116 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | 118 Participants |
| Part 1: DS-8201a Medium Dose | Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | 37 Participants |
| Part 1: DS-8201a High Dose | Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | 18 Participants |
Secondary
Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)
TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.
Time frame: Day 0 to Day 47 post last dose
Population: Adverse event data were assessed in the Safety Analysis Set t data cut-off date of 21 March 2019.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug discontinuation | 6 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with death | 0 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs | 50 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug interruption | 17 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any serious TEAE | 11 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose reduction | 13 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any TEAE | 50 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with drug discontinuation | 6 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose interruption | 19 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related serious TEAEs | 6 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with death | 1 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs of CTCAE ≥Grade 3 | 26 Participants |
| Part 1 and Part 2a: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with dose reduction | 11 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs of CTCAE ≥Grade 3 | 32 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with drug discontinuation | 6 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug discontinuation | 6 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs | 47 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with death | 1 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose reduction | 19 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any TEAE | 48 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug interruption | 13 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any serious TEAE | 6 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with dose reduction | 18 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose interruption | 16 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related serious TEAEs | 4 Participants |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with death | 0 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with drug discontinuation | 8 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any TEAE | 21 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs | 21 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs of CTCAE ≥Grade 3 | 16 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any serious TEAE | 8 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related serious TEAEs | 5 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug discontinuation | 8 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose reduction | 11 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with dose reduction | 11 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose interruption | 12 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug interruption | 11 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with death | 2 Participants |
| Part 1: DS-8201a Medium Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with death | 1 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any serious TEAE | 25 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug interruption | 29 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any TEAE | 129 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose interruption | 36 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs | 128 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with death | 2 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related serious TEAEs | 10 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with death | 8 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug discontinuation | 7 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with dose reduction | 20 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with drug discontinuation | 8 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs of CTCAE ≥Grade 3 | 48 Participants |
| Part 1: DS-8201a High Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose reduction | 21 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with death | 0 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose reduction | 3 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any TEAE | 4 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with dose reduction | 3 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Any serious TEAE | 0 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with dose interruption | 2 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs of CTCAE ≥Grade 3 | 3 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs associated with death | 0 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug interruption | 2 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related TEAEs | 4 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | TEAEs associated with drug discontinuation | 1 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Related TEAEs associated with drug discontinuation | 1 Participants |
| Part 2b (Exploratory): DS-8201a Low Dose | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) | Drug-related serious TEAEs | 0 Participants |
Secondary
Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.
Time frame: Baseline up to Week 6, 12, 18, 24, 30, 36 post dose
Population: Best percent change from baseline in sum of diameters was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 and Part 2a: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 30 | -59.1 Percent change from baseline | Standard Deviation 26.1 |
| Part 1 and Part 2a: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 24 | -56.3 Percent change from baseline | Standard Deviation 22.1 |
| Part 1 and Part 2a: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 18 | -50.1 Percent change from baseline | Standard Deviation 22.1 |
| Part 1 and Part 2a: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Best percent change from baseline | -59.5 Percent change from baseline | Standard Deviation 28.2 |
| Part 1 and Part 2a: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 36 | -61.0 Percent change from baseline | Standard Deviation 26.7 |
| Part 1 and Part 2a: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 12 | -39.6 Percent change from baseline | Standard Deviation 22.7 |
| Part 1 and Part 2a: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 6 | -26.2 Percent change from baseline | Standard Deviation 18.3 |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 36 | -54.6 Percent change from baseline | Standard Deviation 32.2 |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 6 | -32.9 Percent change from baseline | Standard Deviation 25.4 |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 12 | -43.6 Percent change from baseline | Standard Deviation 28.1 |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 18 | -58.5 Percent change from baseline | Standard Deviation 29.4 |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 24 | -61.9 Percent change from baseline | Standard Deviation 32 |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 30 | -63.9 Percent change from baseline | Standard Deviation 32.2 |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Best percent change from baseline | -65.3 Percent change from baseline | Standard Deviation 27.7 |
| Part 1: DS-8201a Medium Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 12 | -39.9 Percent change from baseline | Standard Deviation 24.5 |
| Part 1: DS-8201a Medium Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 36 | -55.5 Percent change from baseline | Standard Deviation 29.9 |
| Part 1: DS-8201a Medium Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Best percent change from baseline | -50.5 Percent change from baseline | Standard Deviation 28.3 |
| Part 1: DS-8201a Medium Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 6 | -26.9 Percent change from baseline | Standard Deviation 21.6 |
| Part 1: DS-8201a Medium Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 18 | -44.4 Percent change from baseline | Standard Deviation 27.8 |
| Part 1: DS-8201a Medium Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 30 | -51.2 Percent change from baseline | Standard Deviation 29.2 |
| Part 1: DS-8201a Medium Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 24 | -49.2 Percent change from baseline | Standard Deviation 30.6 |
| Part 1: DS-8201a High Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 12 | -40.1 Percent change from baseline | Standard Deviation 24.9 |
| Part 1: DS-8201a High Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 24 | -49.3 Percent change from baseline | Standard Deviation 30.5 |
| Part 1: DS-8201a High Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 30 | -51.5 Percent change from baseline | Standard Deviation 29.2 |
| Part 1: DS-8201a High Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 6 | -26.9 Percent change from baseline | Standard Deviation 22.5 |
| Part 1: DS-8201a High Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 36 | -55.5 Percent change from baseline | Standard Deviation 29.9 |
| Part 1: DS-8201a High Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Baseline to Week 18 | -44.9 Percent change from baseline | Standard Deviation 28 |
| Part 1: DS-8201a High Dose | Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | Best percent change from baseline | -50.6 Percent change from baseline | Standard Deviation 28.8 |
Secondary
Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.
Time frame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Population: Progression-free survival was assessed in the Enrolled Analysis Set at data cut-off date of 21 March 2019.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 and Part 2a: DS-8201a Low Dose | Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | NA months |
| Part 1 + Part 2a + Part 2b: DS-8201a Low Dose | Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | 9.5 months |
| Part 1: DS-8201a Medium Dose | Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | NA months |
| Part 1: DS-8201a High Dose | Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) | NA months |