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

Advanced or Metastatic Breast Cancer Clinical Trial

— DB-06  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04494425
• Other study ID #: D9670C00001
• Secondary ID: 2019-004493-26
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 24, 2020
• Est. completion date: June 19, 2026

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 866
• Est. completion date: June 19, 2026
• Est. primary completion date: March 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 105 Years

Eligibility

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)

Related Conditions & MeSH terms

• Advanced or Metastatic Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
• Capecitabine
Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.
• Paclitaxel
Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.
• Nab-Paclitaxel
Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Cordoba
Argentina	Research Site	La Plata
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Australia	Research Site	Adelaide
Australia	Research Site	Birtinya
Australia	Research Site	Darlinghurst
Australia	Research Site	Murdoch
Australia	Research Site	South Brisbane
Australia	Research Site	St Leonards
Australia	Research Site	Waratah
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Belgium	Research Site	Anderlecht
Belgium	Research Site	Bruxelles
Belgium	Research Site	Charleroi
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Belgium	Research Site	Namur
Belgium	Research Site	Roeselare
Belgium	Research Site	Sint-Niklaas
Brazil	Research Site	Barretos
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Natal
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Sorocaba
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	CA
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Baoding
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Dalian
China	Research Site	Foshan
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Jinan
China	Research Site	Linyi
China	Research Site	Nanchang
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Xi'an
China	Research Site	Zhengzhou
Denmark	Research Site	Aalborg
Denmark	Research Site	Copenhagen Ø
Denmark	Research Site	Odense C
Denmark	Research Site	Vejle
France	Research Site	Avignon Cedex 09
France	Research Site	Besançon
France	Research Site	Bordeaux
France	Research Site	Brest
France	Research Site	Caen Cedex 05
France	Research Site	Dijon
France	Research Site	Le Mans
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Nice
France	Research Site	Paris
France	Research Site	Pierre Benite
France	Research Site	Plerin SUR MER
France	Research Site	Rennes
France	Research Site	Saint Herblain Cedex
France	Research Site	Saint-cloud
France	Research Site	Tours
France	Research Site	Villejuif Cedex
Germany	Research Site	Berlin
Germany	Research Site	Dresden
Germany	Research Site	Freiburg
Germany	Research Site	Hannover
Germany	Research Site	München
Germany	Research Site	München
Germany	Research Site	Münster
Germany	Research Site	Velbert
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Kecskemét
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Szolnok
Hungary	Research Site	Tatabánya
India	Research Site	Bengaluru
India	Research Site	Calicut
India	Research Site	Kolkata
India	Research Site	Marg Jaipur
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Surat
India	Research Site	Thiruvananthapuram
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar-Saba
Israel	Research Site	Petah Tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Tel-Aviv
Italy	Research Site	Aviano
Italy	Research Site	Bergamo
Italy	Research Site	Candiolo
Italy	Research Site	Cona
Italy	Research Site	Genova
Italy	Research Site	Livorno
Italy	Research Site	Messina
Italy	Research Site	Milan
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Parma
Italy	Research Site	Prato
Italy	Research Site	Tricase, Lecce
Italy	Research Site	Udine
Japan	Research Site	Akashi-shi
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Gifu-shi
Japan	Research Site	Hidaka-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Isehara
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Koto-ku
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagoya
Japan	Research Site	Naha-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Nishinomiya-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shizuoka
Japan	Research Site	Tsu-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Alc. Cuauhtémoc
Mexico	Research Site	Guadalajara Jalisco
Mexico	Research Site	Guadalajra
Mexico	Research Site	México
Mexico	Research Site	Mexico City
Mexico	Research Site	Mexico City
Mexico	Research Site	Mexico, D.F.
Mexico	Research Site	Monterrey
Mexico	Research Site	Nuevo Leon
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Breda
Netherlands	Research Site	Hengelo
Netherlands	Research Site	Leeuwarden
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Sittard-Geleen
Poland	Research Site	Bydgoszcz
Poland	Research Site	Koszalin
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Rzeszów
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Russian Federation	Research Site	Krasnodar
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Sankt-Peterburg
Russian Federation	Research Site	Yaroslavl
Saudi Arabia	Research Site	Ar Riya?
Saudi Arabia	Research Site	Dammam
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Singapore	Research Site	Bukit Merah
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	El Palmar
Spain	Research Site	La Coruña
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	San Sebastián
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Sweden	Research Site	Göteborg
Sweden	Research Site	Örebro
Sweden	Research Site	Stockholm
Sweden	Research Site	Uppsala
Sweden	Research Site	Växjö
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Tao-Yuan
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Northwood
United States	Research Site	Aurora	Colorado
United States	Research Site	Austin	Texas
United States	Research Site	Bethesda	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Columbus	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Detroit	Michigan
United States	Research Site	Duarte	California
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kansas City	Kansas
United States	Research Site	Lakewood	Colorado
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madison	Wisconsin
United States	Research Site	Nashville	Tennessee
United States	Research Site	Norfolk	Virginia
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Rochester	Minnesota
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Seattle	Washington
United States	Research Site	Springdale	Arkansas
United States	Research Site	Summit	New Jersey
United States	Research Site	Washington	District of Columbia
United States	Research Site	Westbury	New York

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo

Countries where clinical trial is conducted

United States,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) - in HR+, HER2-low populaton	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.	Until progression or death, assessed up to approximately 60 months
Secondary	Overall Survival (OS) - in HR+, HER2-low population	Defined as the time from randomization to death due to any cause	Until death, assessed up to approximately 60 months
Secondary	Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2-Low and HER2 IHC >0<1+)	PFS by BICR according to RECIST 1.1 in ITT population	Until progression or death, assessed up to approximately 60 months
Secondary	Overall Survival - in intent to treat (ITT) population (HER2-Low and HER2 IHC >0<1+)	OS in the ITT population	Until death, assessed up to approximately 60 months
Secondary	Objective Response Rate (ORR) in HR+, HER-2 low populaton	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.	Until progression, assessed up to approximately 60 months
Secondary	Duration of response (DoR) - in HR+, HER-2 low populaton	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	Until progression, assessed up to approximately 60 months
Secondary	Progression Free Survival by Investigator assessment - in the HR+, HER2-low population	PFS using investigator assessments according to RECIST 1.1 in the HER2-low population	Until progression or death, assessed up to approximately 60 months
Secondary	Objective Response Rate (ORR) in the ITT population	ORR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population	Until progression, assessed up to approximately 60 months
Secondary	Duration of response (DoR) - in the ITT population	DoR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population	Until progression, assessed up to approximately 60 months
Secondary	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	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.	Assessed up to approximately 60 months
Secondary	Safety and tolerability of drugs; number of adverse events (AEs)	Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm	Up to follow-up period, approximately 60 months
Secondary	Serum concentration of trastuzumab deruxtecan	Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration	Up to Cycle 8, approximately Week 24; each cycle is 21 days
Secondary	Immunogenicity of trastuzumab deruxtecan	Percentage of patients who develop ADA for trastuzumab deruxtecan	Up to follow-up period, approximately 60 months
Secondary	Health-related quality of life - EORTC-QLQ-C30	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.	Assessed up to approximately 60 months
Secondary	Time to deterioration in EORTC-QLQ-C30 scores	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.	Assessed up to approximately 60 months
Secondary	Health-related quality of life - EORTC QLQ-BR45	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.	Assessed up to approximately 60 months

External Links

•   AZ Breast Cancer Study Navigators
•   Daiichi Sankyo Contact for Clinical Trial Information Phone: 908-992-6400