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

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ClinicalTrials.gov Identifier: NCT04494425

Recruitment Status : Active, not recruiting

First Posted : July 31, 2020

Last Update Posted : April 12, 2024

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborator:

Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

July 20, 2020

First Posted Date ^ICMJE

July 31, 2020

Last Update Posted Date

April 12, 2024

Actual Study Start Date ^ICMJE

July 24, 2020

Actual Primary Completion Date

March 18, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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.

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

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
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
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
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.
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
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
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
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
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.
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
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
Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 60 months ]
Percentage of patients who develop ADA for trastuzumab deruxtecan
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.
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.
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.

Original Secondary Outcome Measures ^ICMJE

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
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
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
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.
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
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
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
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
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.
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
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
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 EORTC-QLQ-C30
Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 60 months ]
Percentage of patients who develop ADA for trastuzumab deruxtecan
Time to deterioration in EORTC-QLQ-C30 scores [ Time Frame: Assessed up to approximately 60 months ]
Time to deterioration from baseline in EORTC-QLQ-C30 scores
Health-related quality of life - EORTC-QLQ-C45 [ Time Frame: Assessed up to approximately 60 months ]
Change from baseline in the physical functioning subscale of the EORTC-QLQ-C45

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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)

Brief Summary

This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.

Detailed Description

Eligible patients will be those patients who have had disease progression on at least 2 previous lines of endocrine therapies given for the treatment of metastatic disease or disease progression within 6 months of starting first line treatment for metastatic disease with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have historically confirmed HR positive (either estrogen receptor and/or progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC >0 <1+ expression, as determined by central laboratory testing results, advanced or metastatic breast cancer.

The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study consists of 2 independent open label treatment arms: trastuzumab deruxtecan and Investigator's choice chemotherapy (paclitaxel, nab-paclitaxel or capecitabine).

Masking: None (Open Label)
Masking Description:

This study is an open-label study that will be conducted "Sponsor-blind". To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.

Primary Purpose: Treatment

Condition ^ICMJE

Advanced or Metastatic Breast Cancer

Intervention ^ICMJE

Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion

Other Name: DS-8201a; T-DXd
Drug: Capecitabine
Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.
Drug: Paclitaxel
Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.
Drug: Nab-Paclitaxel
Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion

Study Arms ^ICMJE

Experimental: Trastuzumab deruxtecan
Trastuzumab deruxtecan (T-DXd; DS-8201a) arm

Intervention: Drug: Trastuzumab deruxtecan
Active Comparator: Standard of Care
Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
Interventions:
- Drug: Capecitabine
- Drug: Paclitaxel
- Drug: Nab-Paclitaxel

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Actual Enrollment ^ICMJE

866

Original Estimated Enrollment ^ICMJE

850

Estimated Study Completion Date ^ICMJE

June 19, 2026

Actual Primary Completion Date

March 18, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Key Inclusion 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

Key Exclusion 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)

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 105 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Russian Federation, Saudi Arabia, Singapore, Spain, Sweden, Taiwan, United Kingdom, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04494425

Other Study ID Numbers ^ICMJE

D9670C00001
2019-004493-26 ( EudraCT Number )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	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
Supporting Materials:	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