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

NCT ID: NCT04494425

Last Updated: 2025-06-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

866 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-24

Study Completion Date

2026-06-19

Brief Summary

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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

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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.

Conditions

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Advanced or Metastatic Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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

TREATMENT

Blinding Strategy

NONE

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.

Study Groups

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Trastuzumab deruxtecan

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

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

Trastuzumab deruxtecan by intravenous infusion

Standard of Care

Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm

Group Type ACTIVE_COMPARATOR

Capecitabine

Intervention Type DRUG

Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.

Paclitaxel

Intervention Type DRUG

Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.

Nab-Paclitaxel

Intervention Type DRUG

Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion

Interventions

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Trastuzumab deruxtecan

Trastuzumab deruxtecan by intravenous infusion

Intervention Type DRUG

Capecitabine

Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.

Intervention Type DRUG

Paclitaxel

Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.

Intervention Type DRUG

Nab-Paclitaxel

Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion

Intervention Type DRUG

Other Intervention Names

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DS-8201a; T-DXd

Eligibility Criteria

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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

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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

105 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Scottsdale, Arizona, United States

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Springdale, Arkansas, United States

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Duarte, California, United States

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Los Angeles, California, United States

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Aurora, Colorado, United States

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Lakewood, Colorado, United States

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Washington D.C., District of Columbia, United States

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Jacksonville, Florida, United States

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Kansas City, Kansas, United States

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Louisville, Kentucky, United States

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Bethesda, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Summit, New Jersey, United States

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Westbury, New York, United States

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Columbus, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Norfolk, Virginia, United States

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Seattle, Washington, United States

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Madison, Wisconsin, United States

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Buenos Aires, , Argentina

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CABA, , Argentina

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CABA, , Argentina

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CABA, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Córdoba, , Argentina

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La Plata, , Argentina

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Mar del Plata, , Argentina

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Rosario, , Argentina

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Rosario, , Argentina

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Adelaide, , Australia

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Birtinya, , Australia

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Darlinghurst, , Australia

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Murdoch, , Australia

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South Brisbane, , Australia

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St Leonards, , Australia

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Waratah, , Australia

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Graz, , Austria

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Innsbruck, , Austria

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Anderlecht, , Belgium

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Brussels, , Belgium

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Charleroi, , Belgium

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Edegem, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Namur, , Belgium

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Roeselare, , Belgium

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Sint-Niklaas, , Belgium

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Barretos, , Brazil

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Belo Horizonte, , Brazil

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Natal, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Sorocaba, , Brazil

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Toronto, CA, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Baoding, , China

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Beijing, , China

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Dalian, , China

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Linyi, , China

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Nanjing, , China

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Nanjing, , China

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Nanning, , China

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Shanghai, , China

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Shenyang, , China

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Tianjin, , China

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Ürümqi, , China

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Wuhan, , China

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Xi'an, , China

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Xi'an, , China

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Zhengzhou, , China

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Aalborg, , Denmark

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Copenhagen Ø, , Denmark

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Odense, , Denmark

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Vejle, , Denmark

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Avignon, , France

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Besançon, , France

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Bordeaux, , France

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Brest, , France

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Caen, , France

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Dijon, , France

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Le Mans, , France

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Marseille, , France

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Montpellier, , France

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Nice, , France

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Pierre-Bénite, , France

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Plerin SUR MER, , France

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Rennes, , France

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Saint-Cloud, , France

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Saint-Herblain, , France

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Tours, , France

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Villejuif, , France

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Berlin, , Germany

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Dresden, , Germany

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Freiburg im Breisgau, , Germany

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Hanover, , Germany

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München, , Germany

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München, , Germany

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Münster, , Germany

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Velbert, , Germany

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Budapest, , Hungary

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Győr, , Hungary

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Kecskemét, , Hungary

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Nyíregyháza, , Hungary

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Szolnok, , Hungary

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Tatabánya, , Hungary

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Bengaluru, , India

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Haifa, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Aviano, , Italy

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Bergamo, , Italy

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Candiolo, , Italy

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Cona, , Italy

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Genova, , Italy

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Livorno, , Italy

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Tricase, Lecce, , Italy

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Udine, , Italy

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Akashi-shi, , Japan

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Bunkyō City, , Japan

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Chiba, , Japan

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Chūōku, , Japan

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Fukuoka, , Japan

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Gifu, , Japan

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Hidaka-shi, , Japan

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Hiroshima, , Japan

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Isehara, , Japan

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Kagoshima, , Japan

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Kashiwa, , Japan

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Kawasaki-shi, , Japan

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Kitaadachi-gun, , Japan

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Kōtoku, , Japan

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Matsuyama, , Japan

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Nagoya, , Japan

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Naha, , Japan

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Niigata, , Japan

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Nishinomiya-shi, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Sagamihara-shi, , Japan

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Sapporo, , Japan

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Shinagawa-ku, , Japan

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Shinjuku-ku, , Japan

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Shizuoka, , Japan

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Tsu, , Japan

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Yokohama, , Japan

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Alc. Cuauhtémoc, , Mexico

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Guadalajara Jalisco, , Mexico

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Guadalajra, , Mexico

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Mexico City, , Mexico

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Mexico City, , Mexico

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Mexico City, , Mexico

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México, , Mexico

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Monterrey, , Mexico

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Nuevo León, , Mexico

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Amsterdam, , Netherlands

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Breda, , Netherlands

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Hengelo, , Netherlands

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Leeuwarden, , Netherlands

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Rotterdam, , Netherlands

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Sittard-Geleen, , Netherlands

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Bydgoszcz, , Poland

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Koszalin, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Rzeszów, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Lisbon, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Krasnodar, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Yaroslavl, , Russia

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Dammam, , Saudi Arabia

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Jeddah, , Saudi Arabia

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Jeddah, , Saudi Arabia

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Riyadh, , Saudi Arabia

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Riyadh, , Saudi Arabia

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Riyadh, , Saudi Arabia

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Bukit Merah, , Singapore

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Singapore, , Singapore

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Singapore, , Singapore

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Singapore, , Singapore

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Singapore, , Singapore

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Daegu, , South Korea

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Goyang-si, , South Korea

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Incheon, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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A Coruña, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Córdoba, , Spain

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El Palmar, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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San Sebastián, , Spain

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Seville, , Spain

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Valencia, , Spain

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Gothenburg, , Sweden

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Örebro, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Vaxjo, , Sweden

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Cambridge, , United Kingdom

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Cardiff, , United Kingdom

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Edinburgh, , United Kingdom

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Guildford, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Northwood, , United Kingdom

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Countries

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

References

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Bardia A, Hu X, Dent R, Yonemori K, Barrios CH, O'Shaughnessy JA, Wildiers H, Pierga JY, Zhang Q, Saura C, Biganzoli L, Sohn J, Im SA, Levy C, Jacot W, Begbie N, Ke J, Patel G, Curigliano G; DESTINY-Breast06 Trial Investigators. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med. 2024 Dec 5;391(22):2110-2122. doi: 10.1056/NEJMoa2407086. Epub 2024 Sep 15.

Reference Type DERIVED
PMID: 39282896 (View on PubMed)

Tarantino P, Tolaney SM, Curigliano G. Trastuzumab deruxtecan (T-DXd) in HER2-low metastatic breast cancer treatment. Ann Oncol. 2023 Oct;34(10):949-950. doi: 10.1016/j.annonc.2023.07.003. Epub 2023 Jul 26. No abstract available.

Reference Type DERIVED
PMID: 37499870 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2023-505554-18-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2019-004493-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D9670C00001

Identifier Type: -

Identifier Source: org_study_id

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