Japanease

Nov. 25, 2020

Jan. 13, 2021

jRCT2061200028

A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive Breast Cancer Patients whose Disease has Progressed on Endocrine Therapy in the Metastatic Setting
(DESTINY-Breast06)

Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer (DB-06)
(DESTINY-Breast06)

Nagao Kiminori

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Dec. 15, 2020

850

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

Argentina/Australia/Belgium/Brazil/Canada/ China/Denmark/France/Germany/Hungary/Italy/Korea/Republic of Mexico/Netherlands/Russian Federation/Saudi Arabia/Spain/Sweden/Taiwan/United States

- Patients must be >=18 years of age (>= 20 years of age - applicable for Japan only)
- Pathologically documented breast cancer that:
1. is advanced or metastatic
2. has a history of HER2-low or negative expression 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
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
- Either disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting or disease progression within 24 months of starting adjuvant endocrine therapy and on at least 1 previous line of endocrine therapy in the metastatic setting
- Has protocol-defined adequate organ and bone marrow function

- Ineligible for all options in the investigator's choice chemotherapy arm
- Lung-specific intercurrent clinically significant illnesses
- Uncontrolled or significant cardiovascular disease or infection
- Active or prior documented interstitial lung disease (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

20age old over
105age old under

Both

Advanced or Metastatic Breast Cancer

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

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.

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.

Recruiting

DAIICHI SANKYO Co.,Ltd.
AstraZeneca
Applicable
Hiroshima City Hiroshima Citizens Hospital Institutional Review Board
7-33 Motomachi, Naka-ku, Hiroshima-shi, Hiroshima

+81-82-221-2291

Approval

Oct. 28, 2020

Yes

Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Supporting Materials: Study Protocol Statistical Analysis Plan (SAP) Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

NCT04494425
ClinicalTrials.gov