Description:
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
Title
- 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]
- 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
Clinical Trial IDs
- ORG STUDY ID:
DS8201-A-U303
- SECONDARY ID:
2018-003069-33
- SECONDARY ID:
184223
- SECONDARY ID:
DESTINY-B04
- NCT ID:
NCT03734029
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Trastuzumab deruxtecan (DS-8201a) | DS-8201a | Trastuzumab deruxtecan |
Capecitabine | | Physician's Choice |
Eribulin | | Physician's Choice |
Gemcitabine | | Physician's Choice |
Paclitaxel | | Physician's Choice |
Nab-paclitaxel | | Physician's Choice |
Purpose
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
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Trastuzumab deruxtecan | Experimental | HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a | - Trastuzumab deruxtecan (DS-8201a)
|
Physician's Choice | Active Comparator | HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options:
Capecitabine
Eribulin
Gemcitabine
Paclitaxel
Nab-paclitaxel | - Capecitabine
- Eribulin
- Gemcitabine
- Paclitaxel
- Nab-paclitaxel
|
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
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 protocol-defined measurable lesion
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) |
Time Frame: | within approximately 3 years |
Safety Issue: | |
Description: | Time from the date of randomization to the earliest date of the first objective documentation of radiographic disease progression via blinded independent central review (BICR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1 or death due to any cause. |
Secondary Outcome Measures
Measure: | PFS based on Investigator Assessment |
Time Frame: | within approximately 3 years |
Safety Issue: | |
Description: | Time from the date of randomization to the first objective documentation of radiographic disease progression via investigator assessment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1 or death due to any cause. |
Measure: | Overall Survival (OS) |
Time Frame: | within approximately 3 years |
Safety Issue: | |
Description: | Time from the date of randomization to the date of death for any cause. If there is no death reported for a participant before the data cutoff for OS analysis, OS will be censored at the last contact date at which the participant is known to be alive. |
Measure: | Objective Response Rate (ORR) |
Time Frame: | within approximately 3 years |
Safety Issue: | |
Description: | Percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR), confirmed by a second assessment. |
Measure: | Duration of Response (DoR), Based on Blinded Independent Central Review (BICR) and Investigator Assessment |
Time Frame: | within approximately 3 years |
Safety Issue: | |
Description: | DoR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Daiichi Sankyo, Inc. |
Trial Keywords
- Anti-HER2-Antibody Drug Conjugate (ADC)
- Unresectable or Metastatic
- Human epidermal growth factor receptor 2 (HER2)-low
- DESTINY - Breast 04
Last Updated
January 11, 2021