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.
Active, not recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| DS-8201a | Experimental product | DS-8201a High Dose |
| Name | Type | Description | Interventions |
|---|---|---|---|
| DS-8201a Low Dose | Experimental | T-DM1 resistant/refractory (R/R) patients in the low dose treatment group |
|
| DS-8201a Medium Dose | Experimental | T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group |
|
| DS-8201a High Dose | Experimental | T-DM1 resistant/refractory (R/R) patients in the high dose treatment group |
|
| Exploratory Arm | Other | In Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm |
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | 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) |
| Time Frame: | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) |
| Time Frame: | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set) |
| Time Frame: | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Time Frame: | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Time Frame: | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Time Frame: | at least 6 months after last participant enrolled received first dose up to 19 months (data cut off) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Time Frame: | Baseline up to Week 6, 12, 18, 24, 30, 36 post dose |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set) |
| Time Frame: | Day 0 to Day 47 post last dose |
| Safety Issue: | |
| Description: | 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. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Daiichi Sankyo, Inc. |
May 26, 2021
