Brief Summary
This study will compare DS-8201a to physician choice standard treatment.
Participants must have HER2-low breast cancer that has been treated before.
Participants' cancer:
* Cannot be removed by an operation
* Has spread to other parts of the body
Participants must have HER2-low breast cancer that has been treated before.
Participants' cancer:
* Cannot be removed by an operation
* Has spread to other parts of the body
Brief Title
Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]
Detailed Description
This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer participants.
The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.
The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Breast Cancer
Eligibility Criteria
Inclusion Criteria:
* Is the age of majority in their country
* Has pathologically documented breast cancer that:
1. Is unresectable or metastatic
2. Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
3. Is HR-positive or HR-negative
4. Has progressed on, and would no longer benefit from, endocrine therapy
5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting
6. Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists \[ASCO-CAP\] guidelines)
* Has documented radiologic progression (during or after most recent treatment)
* Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for:
1. assessment of HER2 status
2. assessment of post-treatment status
* Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1
* Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions
* Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)
Exclusion Criteria:
* Is ineligible for all options in the physician's choice arm
* Has breast cancer ever assessed with high-HER2 expression
* Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate
* Has uncontrolled or significant cardiovascular disease
* Has spinal cord compression or clinically active central nervous system metastases
* Has 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 any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study
* Is the age of majority in their country
* Has pathologically documented breast cancer that:
1. Is unresectable or metastatic
2. Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
3. Is HR-positive or HR-negative
4. Has progressed on, and would no longer benefit from, endocrine therapy
5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting
6. Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists \[ASCO-CAP\] guidelines)
* Has documented radiologic progression (during or after most recent treatment)
* Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for:
1. assessment of HER2 status
2. assessment of post-treatment status
* Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1
* Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions
* Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)
Exclusion Criteria:
* Is ineligible for all options in the physician's choice arm
* Has breast cancer ever assessed with high-HER2 expression
* Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate
* Has uncontrolled or significant cardiovascular disease
* Has spinal cord compression or clinically active central nervous system metastases
* Has 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 any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study
Inclusion Criteria
Inclusion Criteria:
* Is the age of majority in their country
* Has pathologically documented breast cancer that:
1. Is unresectable or metastatic
2. Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
3. Is HR-positive or HR-negative
4. Has progressed on, and would no longer benefit from, endocrine therapy
5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting
6. Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists \[ASCO-CAP\] guidelines)
* Has documented radiologic progression (during or after most recent treatment)
* Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for:
1. assessment of HER2 status
2. assessment of post-treatment status
* Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1
* Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions
* Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)
* Is the age of majority in their country
* Has pathologically documented breast cancer that:
1. Is unresectable or metastatic
2. Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
3. Is HR-positive or HR-negative
4. Has progressed on, and would no longer benefit from, endocrine therapy
5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting
6. Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists \[ASCO-CAP\] guidelines)
* Has documented radiologic progression (during or after most recent treatment)
* Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for:
1. assessment of HER2 status
2. assessment of post-treatment status
* Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1
* Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions
* Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)
Gender
All
Gender Based
false
Keywords
Anti-HER2-Antibody Drug Conjugate (ADC)
Unresectable or Metastatic
Human epidermal growth factor receptor 2 (HER2)-low
DESTINY - Breast 04
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03734029
Org Class
Industry
Org Full Name
Daiichi Sankyo
Org Study Id
DS8201-A-U303
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects
Primary Outcomes
Outcome Description
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Outcome Measure
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Outcome Time Frame
From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Secondary Ids
Secondary Id
2018-003069-33
Secondary Id
184223
Secondary Id
DESTINY-B04
Secondary Outcomes
Outcome Description
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Outcome Time Frame
From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Outcome Measure
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status
Outcome Description
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Outcome Time Frame
From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Outcome Measure
Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Outcome Description
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Outcome Time Frame
From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Outcome Measure
Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients)
Outcome Description
Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.
Outcome Time Frame
From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Outcome Measure
Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Outcome Time Frame
From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Outcome Measure
Number of Overall Survival Events (Deaths)
Outcome Description
Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.
Outcome Time Frame
From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Outcome Measure
Overall Survival (OS) in All Patients
Outcome Description
Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment.
Outcome Time Frame
From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years
Outcome Measure
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Outcome Description
Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment.
Outcome Time Frame
From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years
Outcome Measure
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients)
Outcome Description
Duration of Response (DoR) is defined as the date of the first documented objective response (complete response \[CR\] or partial response \[PR\]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Outcome Time Frame
From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years
Outcome Measure
Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Outcome Description
Duration of Response (DoR) is defined as the date of the first documented objective response (complete response \[CR\] or partial response \[PR\]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Outcome Time Frame
From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years
Outcome Measure
Duration of Response in Participants With HER2-low Breast Cancer (All Patients)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sun Young Oh
Investigator Email
suyoung@montefiore.org
Investigator Phone
918-405-8404