Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer (DB-06)

JRCT ID: jRCT2061200028

Registered date:25/11/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Advanced or Metastatic Breast Cancer
• Date of first enrollment: 21/12/2020
• Target sample size: 850
• Countries of recruitment: Argentina,Japan,Australia,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Denmark,Japan,France,Japan,Germany,Japan,Hungary,Japan,Italy,Japan,South Korea,Japan,Mexico,Japan,Netherlands,Japan,Russia,Japan,Saudi Arabia,Japan,Spain,Japan,Sweden,Japan,Taiwan,Japan,United States,Japan,United Kingdom,Japan,Singapore,Japan,Poland,Japan,Israel,Japan,India,Japan,Austria,Japan,Portugal,Japan
• Study type: Interventional

Intervention(s)

Trastuzumab deruxtecan (T-DXd; DS-8201a) arm
- Trastuzumab deruxtecan by intravenous infusion

Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
- Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.
- Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.
- Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion

Outcome(s)

Primary Outcome

Progression Free Survival (PFS) - in HR+, HER2-low populaton [ Time Frame: Until progression or death, assessed up to approximately 60 months ]
Defined as time from date of randomization until the date of objective radiological disease progression by blinded independent central review (BICR) assessment according to RECIST 1.1 or death.

Secondary Outcome

1. Overall Survival (OS) - in HR+, HER2-low population [ Time Frame: Until death, assessed up to approximately 60 months ]
Defined as the time from randomization to death due to any cause
2. Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2-Low and HER2 IHC >0<1+) [ Time Frame: Until progression or death, assessed up to approximately 60 months ]
PFS by BICR according to RECIST 1.1 in ITT population
3. Overall Survival - in intent to treat (ITT) population (HER2-Low and HER2 IHC >0<1+) [ Time Frame: Until death, assessed up to approximately 60 months ]
OS in the ITT population
4. Objective Response Rate (ORR) in HR+, HER-2 low populaton [ Time Frame: Until progression, assessed up to approximately 60 months ]
ORR defined as the percentage of patients with at least one visit response of complete or partial response (CR or PR) by BICR and Investigator assessment according to RECIST 1.1.
5. Duration of response (DoR) - in HR+, HER-2 low populaton [ Time Frame: Until progression, assessed up to approximately 60 months ]
DoR defined as the time from the date of first documented response (CR/PR) until the first progression or death in the absence of disease progression by BICR and Investigator assessment according to RECIST 1.1
6. Progression Free Survival by Investigator assessment - in the HR+, HER2-low population [ Time Frame: Until progression or death, assessed up to approximately 60 months ]
PFS using investigator assessments according to RECIST 1.1 in the HER2-low population
7. Objective Response Rate (ORR) in the ITT population [ Time Frame: Until progression, assessed up to approximately 60 months ]
ORR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
8. Duration of response (DoR) - in the ITT population [ Time Frame: Until progression, assessed up to approximately 60 months ]
DoR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
9. PFS2 by Investigator assessment, time to first subsequent therapy (TFST) and time to second subsequent treatment or death (TSST) - in HR+, HER2-low and the ITT population [ Time Frame: Assessed up to approximately 60 months ]
PFS2 defined as time from randomisation to second progression or death. TFST defined as a time elapsed from randomization to first subsequent therapy or death. TSST defined as a time elapsed from randomization to second subsequent therapy or death.
10. Safety and tolerability of drugs; number of adverse events (AEs) [ Time Frame: Up to follow-up period, approximately 60 months ]
Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm
11. Serum concentration of trastuzumab deruxtecan [ Time Frame: Up to Cycle 8, approximately Week 24; each cycle is 21 days ]
Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
12. Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 60 months ]
Percentage of patients who develop ADA for trastuzumab deruxtecan
13. Health-related quality of life - EORTC-QLQ-C30 [ Time Frame: Assessed up to approximately 60 months ]
Change from baseline in the physical functioning subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
14. Time to deterioration in EORTC-QLQ-C30 scores [ Time Frame: Assessed up to approximately 60 months ]
Time to deterioration from baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
15.Health-related quality of life - EORTC QLQ-BR45 [ Time Frame: Assessed up to approximately 60 months ]
Change from baseline in the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR45) score. Scale scores range from 0-100. For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 105age old
• Gender: Both

Include criteria

- Patients must be >=18 years of age
- Pathologically documented breast cancer that:
1.is advanced or metastatic
2.has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
3.has HER2-low or HER2 IHC >0 <1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting
4.was never previously HER2-positive
5.is documented HR+ disease in the metastatic setting.
- No prior chemotherapy for advanced or metastatic breast cancer.
- Has adequate tumor samples for assessment of HER2 status
- Must have either:
1.disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
2.disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the >=2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.
- Has protocol-defined adequate organ and bone marrow function

Exclude criteria

- Ineligible for all options in the investigator's choice chemotherapy arm
- Lung-specific intercurrent clinically significant illnesses
- Uncontrolled or significant cardiovascular disease or infection
- Prior documented interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- Patients with spinal cord compression or clinically active central nervous system metastases
- Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT04494425