Clinical Trials /

A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)

NCT03248492

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT03248492

Trial Eligibility

Document

Title

  • Brief Title: A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)
  • Official Title: A Phase 2, Multicenter, Open-Label Study of DS-8201a, an Anti-HER2-Antibody Drug Conjugate (ADC) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1 (DESTINY-Breast01)

Clinical Trial IDs

  • ORG STUDY ID: DS8201-A-U201
  • SECONDARY ID: 2016-004986-18
  • SECONDARY ID: JapicCTI-173693(en)
  • SECONDARY ID: DESTINY-Breast01
  • NCT ID: NCT03248492

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
DS-8201aExperimental productDS-8201a High Dose

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
DS-8201a Low DoseExperimentalT-DM1 resistant/refractory (R/R) patients in the low dose treatment group
  • DS-8201a
DS-8201a Medium DoseExperimentalT-DM1 resistant/refractory (R/R) patients in the medium dose treatment group
  • DS-8201a
DS-8201a High DoseExperimentalT-DM1 resistant/refractory (R/R) patients in the high dose treatment group
  • DS-8201a
Exploratory ArmOtherIn Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm
  • DS-8201a

Eligibility Criteria

        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

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • HER-2 positive breast cancer
  • Metastatic or Unresectable
  • Resistant or refractory to T-DM1
  • DESTINY - Breast 01
  • Trastuzumab deruxtecan
  • T-DXd

Last Updated

May 26, 2021