Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)

NCT ID: NCT04784715

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1157 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-26

Study Completion Date

2029-12-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment in the metastatic setting.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Eligible participants will be those diagnosed with HER2-positive (IHC 3+ or ISH+), metastatic breast cancer, who have received no prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer.

The study aims to evaluate the efficacy, and safety of trastuzumab deruxtecan, alone or with pertuzumab, compared with the standard of care treatment (taxane \[docetaxel or paclitaxel\], trastuzumab and pertuzumab). 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

See the medical conditions and disease areas that this research is targeting or investigating.

Breast Cancer; HER2-positive; Metastatic

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Breast Neoplasms; Breast Diseases; Trastuzumab; Antineoplastic Agents, Phytogenic; Anti-drug conjugate; Molecular Mechanisms of Pharmacological Action;

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Study will consist of three arms:

Arm A - trastuzumab deruxtecan with pertuzumab-matching placebo Arm B - trastuzumab deruxtecan with pertuzumab Arm C - standard of care (taxane \[docetaxel or paclitaxel\], trastuzumab and pertuzumab)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

This study is open-label with respect to the control arm. Pertuzumab/placebo in the experimental arms will be blinded to the investigator and patients.

The study will be "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

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm A

Trastuzumab deruxtecan (T-DXd) plus pertuzumab-matching placebo

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

Administered by intravenous infusion

Placebo

Intervention Type DRUG

Administered by intravenous infusion

Arm B

Trastuzumab deruxtecan (T-DXd) plus pertuzumab

Group Type EXPERIMENTAL

Trastuzumab deruxtecan

Intervention Type DRUG

Administered by intravenous infusion

Pertuzumab

Intervention Type DRUG

Administered by intravenous infusion

Arm C

Standard of care (Taxane (paclitaxel or docetaxel), trastuzumab, and pertuzumab)

Group Type ACTIVE_COMPARATOR

Taxane

Intervention Type DRUG

Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion

Pertuzumab

Intervention Type DRUG

Administered by intravenous infusion

Trastuzumab

Intervention Type DRUG

Administered by intravenous infusion

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Trastuzumab deruxtecan

Administered by intravenous infusion

Intervention Type DRUG

Placebo

Administered by intravenous infusion

Intervention Type DRUG

Taxane

Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion

Intervention Type DRUG

Pertuzumab

Administered by intravenous infusion

Intervention Type DRUG

Trastuzumab

Administered by intravenous infusion

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

DS-8201a; T-DXd

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients must be ≥18 years of age
* Pathologically documented breast cancer that:

1. is advanced or metastatic
2. is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+)
3. is documented by local testing as hormone receptor (HR)-positive or HR-negative disease in the metastatic setting
* No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer or only 1 previous line of endocrine therapy in the metastatic setting. Participants who have received chemotherapy or HER2-targeted therapy in the neo-adjuvant or adjuvant setting are eligible if \> 6 months from treatment to metastatic diagnosis.
* Has protocol-defined adequate organ and bone marrow function
* ECOG performance status 0 or 1

Exclusion Criteria

* Ineligible for any of the agents on the study.
* Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with subject's participation or study results
* Patients with spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic may be included in the study.
* Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
* Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Daiichi Sankyo

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Research Site

Tucson, Arizona, United States

Site Status

Research Site

Springdale, Arkansas, United States

Site Status

Research Site

Glendale, California, United States

Site Status

Research Site

Glendale, California, United States

Site Status

Research Site

Longmont, Colorado, United States

Site Status

Research Site

Miami, Florida, United States

Site Status

Research Site

Palm Bay, Florida, United States

Site Status

Research Site

Plantation, Florida, United States

Site Status

Research Site

Atlanta, Georgia, United States

Site Status

Research Site

Louisville, Kentucky, United States

Site Status

Research Site

Silver Spring, Maryland, United States

Site Status

Research Site

Boston, Massachusetts, United States

Site Status

Research Site

Detroit, Michigan, United States

Site Status

Research Site

Jackson, Mississippi, United States

Site Status

Research Site

Las Vegas, Nevada, United States

Site Status

Research Site

Summit, New Jersey, United States

Site Status

Research Site

New York, New York, United States

Site Status

Research Site

Shirley, New York, United States

Site Status

Research Site

York, Pennsylvania, United States

Site Status

Research Site

Germantown, Tennessee, United States

Site Status

Research Site

Dallas, Texas, United States

Site Status

Research Site

Dallas, Texas, United States

Site Status

Research Site

Denton, Texas, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

San Antonio, Texas, United States

Site Status

Research Site

Shenandoah, Texas, United States

Site Status

Research Site

Tyler, Texas, United States

Site Status

Research Site

Norfolk, Virginia, United States

Site Status

Research Site

Roanoke, Virginia, United States

Site Status

Research Site

Tacoma, Washington, United States

Site Status

Research Site

Buenos Aires, , Argentina

Site Status

Research Site

CABA, , Argentina

Site Status

Research Site

CABA, , Argentina

Site Status

Research Site

Caba, , Argentina

Site Status

Research Site

Capital Federal, , Argentina

Site Status

Research Site

Cipolletti, , Argentina

Site Status

Research Site

Ciudad de Buenos Aires, , Argentina

Site Status

Research Site

La Plata, , Argentina

Site Status

Research Site

Mar del Plata, , Argentina

Site Status

Research Site

Rosario, , Argentina

Site Status

Research Site

Rosario, , Argentina

Site Status

Research Site

San Salvador de Jujuy, , Argentina

Site Status

Research Site

Brussels, , Belgium

Site Status

Research Site

Brussels, , Belgium

Site Status

Research Site

Charleroi, , Belgium

Site Status

Research Site

Edegem, , Belgium

Site Status

Research Site

Ghent, , Belgium

Site Status

Research Site

Leuven, , Belgium

Site Status

Research Site

Liège, , Belgium

Site Status

Research Site

Namur, , Belgium

Site Status

Research Site

Florianópolis, , Brazil

Site Status

Research Site

Goiânia, , Brazil

Site Status

Research Site

Londrina, , Brazil

Site Status

Research Site

Natal, , Brazil

Site Status

Research Site

Porto Alegre, , Brazil

Site Status

Research Site

Ribeirão Preto, , Brazil

Site Status

Research Site

São Paulo, , Brazil

Site Status

Research Site

Sorocaba, , Brazil

Site Status

Research Site

Vitória, , Brazil

Site Status

Research Site

Calgary, Alberta, Canada

Site Status

Research Site

Halifax, Nova Scotia, Canada

Site Status

Research Site

Barrie, Ontario, Canada

Site Status

Research Site

Kitchener, Ontario, Canada

Site Status

Research Site

Newmarket, Ontario, Canada

Site Status

Research Site

North York, Ontario, Canada

Site Status

Research Site

Toronto, Ontario, Canada

Site Status

Research Site

Montreal, Quebec, Canada

Site Status

Research Site

Montreal, Quebec, Canada

Site Status

Research Site

Montreal, Quebec, Canada

Site Status

Research Site

Montreal, Quebec, Canada

Site Status

Research Site

Ste-Foy, Quebec, Canada

Site Status

Research Site

Saskatoon, Saskatchewan, Canada

Site Status

Research Site

Beijing, , China

Site Status

Research Site

Beijing, , China

Site Status

Research Site

Beijing, , China

Site Status

Research Site

Changchun, , China

Site Status

Research Site

Changsha, , China

Site Status

Research Site

Changsha, , China

Site Status

Research Site

Chengdu, , China

Site Status

Research Site

Chongqing, , China

Site Status

Research Site

Chongqing, , China

Site Status

Research Site

Dalian, , China

Site Status

Research Site

Guangzhou, , China

Site Status

Research Site

Guangzhou, , China

Site Status

Research Site

Guangzhou, , China

Site Status

Research Site

Hangzhou, , China

Site Status

Research Site

Hangzhou, , China

Site Status

Research Site

Harbin, , China

Site Status

Research Site

Kunming, , China

Site Status

Research Site

Nanchang, , China

Site Status

Research Site

Nanjing, , China

Site Status

Research Site

Nanjing, , China

Site Status

Research Site

Nanning, , China

Site Status

Research Site

Qingdao, , China

Site Status

Research Site

Shanghai, , China

Site Status

Research Site

Shanghai, , China

Site Status

Research Site

Shenyang, , China

Site Status

Research Site

Shenzhen, , China

Site Status

Research Site

Tianjin, , China

Site Status

Research Site

Wuhan, , China

Site Status

Research Site

Wuhan, , China

Site Status

Research Site

Wuhan, , China

Site Status

Research Site

Xi'an, , China

Site Status

Research Site

Xi'an, , China

Site Status

Research Site

Yinchuan, , China

Site Status

Research Site

Zhengzhou, , China

Site Status

Research Site

Copenhagen O, , Denmark

Site Status

Research Site

Sønderborg, , Denmark

Site Status

Research Site

Vejle, , Denmark

Site Status

Research Site

Avignon, , France

Site Status

Research Site

Besançon, , France

Site Status

Research Site

Bordeaux, , France

Site Status

Research Site

Caen, , France

Site Status

Research Site

Le Mans, , France

Site Status

Research Site

Montpellier, , France

Site Status

Research Site

Montpellier, , France

Site Status

Research Site

Nice, , France

Site Status

Research Site

Paris, , France

Site Status

Research Site

Pierre-Bénite, , France

Site Status

Research Site

Rennes, , France

Site Status

Research Site

Saint-Cloud, , France

Site Status

Research Site

Saint-Herblain, , France

Site Status

Research Site

Toulouse, , France

Site Status

Research Site

Vandœuvre-lès-Nancy, , France

Site Status

Research Site

Berlin, , Germany

Site Status

Research Site

Dresden, , Germany

Site Status

Research Site

Erlangen, , Germany

Site Status

Research Site

Essen, , Germany

Site Status

Research Site

Frankfurt am Main, , Germany

Site Status

Research Site

Freiburg im Breisgau, , Germany

Site Status

Research Site

Hamburg, , Germany

Site Status

Research Site

Heidelberg, , Germany

Site Status

Research Site

Leipzig, , Germany

Site Status

Research Site

Münster, , Germany

Site Status

Research Site

Paderborn, , Germany

Site Status

Research Site

Budapest, , Hungary

Site Status

Research Site

Budapest, , Hungary

Site Status

Research Site

Budapest, , Hungary

Site Status

Research Site

Budapest, , Hungary

Site Status

Research Site

Budapest, , Hungary

Site Status

Research Site

Győr, , Hungary

Site Status

Research Site

Kecskemét, , Hungary

Site Status

Research Site

Nyíregyháza, , Hungary

Site Status

Research Site

Szolnok, , Hungary

Site Status

Research Site

Ahmedabad, , India

Site Status

Research Site

Bangalore, , India

Site Status

Research Site

Bengaluru, , India

Site Status

Research Site

Calicut, , India

Site Status

Research Site

Gurgaon, , India

Site Status

Research Site

Mysuru, , India

Site Status

Research Site

Nashik, , India

Site Status

Research Site

Nashik, , India

Site Status

Research Site

New Delhi, , India

Site Status

Research Site

New Delhi, , India

Site Status

Research Site

Haifa, , Israel

Site Status

Research Site

Jerusalem, , Israel

Site Status

Research Site

Petah Tikva, , Israel

Site Status

Research Site

Ramat Gan, , Israel

Site Status

Research Site

Tel Aviv, , Israel

Site Status

Research Site

Bergamo, , Italy

Site Status

Research Site

Candiolo, , Italy

Site Status

Research Site

Genova, , Italy

Site Status

Research Site

Livorno, , Italy

Site Status

Research Site

Milan, , Italy

Site Status

Research Site

Napoli, , Italy

Site Status

Research Site

Padua, , Italy

Site Status

Research Site

Rozzano, , Italy

Site Status

Research Site

Udine, , Italy

Site Status

Research Site

Akashi-shi, , Japan

Site Status

Research Site

Aomori, , Japan

Site Status

Research Site

Bunkyō City, , Japan

Site Status

Research Site

Chiba, , Japan

Site Status

Research Site

Chūōku, , Japan

Site Status

Research Site

Fukushima, , Japan

Site Status

Research Site

Hidaka-shi, , Japan

Site Status

Research Site

Hiroshima, , Japan

Site Status

Research Site

Hiroshima, , Japan

Site Status

Research Site

Isehara-shi, , Japan

Site Status

Research Site

Kagoshima, , Japan

Site Status

Research Site

Kawasaki-shi, , Japan

Site Status

Research Site

Kobe, , Japan

Site Status

Research Site

Kōtoku, , Japan

Site Status

Research Site

Kurume-shi, , Japan

Site Status

Research Site

Kyoto, , Japan

Site Status

Research Site

Matsuyama, , Japan

Site Status

Research Site

Nagoya, , Japan

Site Status

Research Site

Nagoya, , Japan

Site Status

Research Site

Niigata, , Japan

Site Status

Research Site

Nishinomiya-shi, , Japan

Site Status

Research Site

Okayama, , Japan

Site Status

Research Site

Osaka, , Japan

Site Status

Research Site

Ota-shi, , Japan

Site Status

Research Site

Sapporo, , Japan

Site Status

Research Site

Sendai, , Japan

Site Status

Research Site

Shinagawa-ku, , Japan

Site Status

Research Site

Shinjuku-ku, , Japan

Site Status

Research Site

Shinjuku-ku, , Japan

Site Status

Research Site

Shizuoka, , Japan

Site Status

Research Site

Tsu, , Japan

Site Status

Research Site

Yokohama, , Japan

Site Status

Research Site

Alc. Cuauhtémoc, , Mexico

Site Status

Research Site

Estado de México, , Mexico

Site Status

Research Site

Guadalajara, , Mexico

Site Status

Research Site

Metepec, , Mexico

Site Status

Research Site

Nuevo León, , Mexico

Site Status

Research Site

Veracruz, , Mexico

Site Status

Research Site

Arequipa, , Peru

Site Status

Research Site

Lima, , Peru

Site Status

Research Site

Lima, , Peru

Site Status

Research Site

Lima, , Peru

Site Status

Research Site

Lima, , Peru

Site Status

Research Site

Baguio City, , Philippines

Site Status

Research Site

Cebu City, , Philippines

Site Status

Research Site

Davao City, , Philippines

Site Status

Research Site

Iloilo City, , Philippines

Site Status

Research Site

Manila, , Philippines

Site Status

Research Site

Quezon City, , Philippines

Site Status

Research Site

San Juan City, , Philippines

Site Status

Research Site

Bucharest, , Romania

Site Status

Research Site

Floreşti, , Romania

Site Status

Research Site

Moscow, , Russia

Site Status

Research Site

Moscow, , Russia

Site Status

Research Site

Moscow, , Russia

Site Status

Research Site

Saint Petersburg, , Russia

Site Status

Research Site

Saint Petersburg, , Russia

Site Status

Research Site

Yaroslavl, , Russia

Site Status

Research Site

Dammam, , Saudi Arabia

Site Status

Research Site

Jeddah, , Saudi Arabia

Site Status

Research Site

Jeddah, , Saudi Arabia

Site Status

Research Site

Riyadh, , Saudi Arabia

Site Status

Research Site

Riyadh, , Saudi Arabia

Site Status

Research Site

Cape Town, , South Africa

Site Status

Research Site

Cape Town, , South Africa

Site Status

Research Site

George, , South Africa

Site Status

Research Site

Johannesburg, , South Africa

Site Status

Research Site

Johannesburg, , South Africa

Site Status

Research Site

Port Elizabeth, , South Africa

Site Status

Research Site

Pretoria, , South Africa

Site Status

Research Site

Rondebosch, , South Africa

Site Status

Research Site

Soweto, , South Africa

Site Status

Research Site

Cheonan-si, , South Korea

Site Status

Research Site

Daegu, , South Korea

Site Status

Research Site

Goyang-si, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Alicante, , Spain

Site Status

Research Site

Barcelona, , Spain

Site Status

Research Site

Barcelona, , Spain

Site Status

Research Site

Barcelona, , Spain

Site Status

Research Site

Madrid, , Spain

Site Status

Research Site

Madrid, , Spain

Site Status

Research Site

Majadahonda, , Spain

Site Status

Research Site

Seville, , Spain

Site Status

Research Site

Gothenburg, , Sweden

Site Status

Research Site

Örebro, , Sweden

Site Status

Research Site

Stockholm, , Sweden

Site Status

Research Site

Uppsala, , Sweden

Site Status

Research Site

Vaxjo, , Sweden

Site Status

Research Site

Taichung, , Taiwan

Site Status

Research Site

Tainan, , Taiwan

Site Status

Research Site

Taipei, , Taiwan

Site Status

Research Site

Taipei, , Taiwan

Site Status

Research Site

Taipei, , Taiwan

Site Status

Research Site

Taipei, , Taiwan

Site Status

Research Site

Taoyuan District, , Taiwan

Site Status

Research Site

Adana, , Turkey (Türkiye)

Site Status

Research Site

Ankara, , Turkey (Türkiye)

Site Status

Research Site

Ankara, , Turkey (Türkiye)

Site Status

Research Site

Karşıyaka, , Turkey (Türkiye)

Site Status

Research Site

Malatya, , Turkey (Türkiye)

Site Status

Research Site

Samsun, , Turkey (Türkiye)

Site Status

Research Site

Buckhurst Hill, , United Kingdom

Site Status

Research Site

Edinburgh, , United Kingdom

Site Status

Research Site

Guildford, , United Kingdom

Site Status

Research Site

London, , United Kingdom

Site Status

Research Site

Manchester, , United Kingdom

Site Status

Research Site

Swansea, , United Kingdom

Site Status

Research Site

Taunton, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Australia Austria United States Argentina Belgium Brazil Canada China Denmark France Germany Hungary India Israel Italy Japan Mexico Peru Philippines Romania Russia Saudi Arabia South Africa South Korea Spain Sweden Taiwan Turkey (Türkiye) United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Tolaney SM, Jiang Z, Zhang Q, Barroso-Sousa R, Park YH, Rimawi MF, Saura C, Schneeweiss A, Toi M, Chae YS, Kemal Y, Chaudhari M, Sendur MAN, Yamashita T, Casalnuovo M, Danso MA, Liu J, Shetty J, Herbolsheimer P, Loibl S; DESTINY-Breast09 Trial Investigators. Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2025 Oct 29. doi: 10.1056/NEJMoa2508668. Online ahead of print.

Reference Type DERIVED
PMID: 41160818 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://breastcancerstudylocator.com/

BreastCancerStudyLocator.com

http://[email protected]

Daiichi Sankyo Contact for Clinical Trial Information Phone: 908-992-6400

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2023-507904-30-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-004074-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D967UC00001

Identifier Type: -

Identifier Source: org_study_id