A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)

NCT ID: NCT03248492

Last Updated: 2025-06-26

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

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

253 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-25

Study Completion Date

2024-05-06

Brief Summary

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Some human epidermal growth factor receptor 2 (HER-2) breast cancer patients do not respond or become resistant to current treatment. DS-8201a is a new experimental product that is a combination of an antibody and a drug. It has not yet been approved for use. DS-8201a may slow down tumor growth. This might improve outcomes for these patients.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

In Part 1, about 60 trastuzumab emtansine (T-DM1) resistant/refractory patients initially will be randomized into three treatment groups (low, medium and high doses) for Pharmacokinetics (PK), then about another 60 will be randomized into low and high doses to determine recommended dose (RD). After that, about 100 will receive the recommended dose in an open-label continuation stage (Part 2). About 10 TDM-1 intolerant patients will join the continuation stage as an exploratory only arm.

Study Groups

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DS-8201a Low Dose

T-DM1 resistant/refractory (R/R) patients in the low dose treatment group

Group Type EXPERIMENTAL

DS-8201a

Intervention Type DRUG

DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.

DS-8201a Medium Dose

T-DM1 resistant/refractory (R/R) patients in the medium dose treatment group

Group Type EXPERIMENTAL

DS-8201a

Intervention Type DRUG

DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.

DS-8201a High Dose

T-DM1 resistant/refractory (R/R) patients in the high dose treatment group

Group Type EXPERIMENTAL

DS-8201a

Intervention Type DRUG

DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.

Exploratory Arm

In Part 2b- Continuation Stage, about 10 T-DM1 Intolerant patients will receive the DS-8201a recommended dose (RD) as an exploratory arm

Group Type OTHER

DS-8201a

Intervention Type DRUG

DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.

Interventions

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DS-8201a

DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as low, medium and high intravenous (IV) doses for Part 1 of the trial. The dose for Part 2 will be determined based on results from Part 1.

Intervention Type DRUG

Other Intervention Names

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Experimental product

Eligibility Criteria

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Inclusion Criteria

* Men or women the age of majority in their country
* Has pathologically documented breast cancer that:

1. is unresectable or metastatic
2. has HER2 positive expression confirmed per protocol
* Has an adequate tumor sample
* Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Has protocol-defined adequate cardiac, renal and hepatic function
* Agrees to follow protocol-defined method(s) of contraception

Exclusion Criteria

* Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia
* Has a corrected QT interval (QTc) prolongation to \> 450 millisecond (ms) in males and \> 470 ms in females
* Has a medical history of clinically significant lung disease
* Is suspected to have certain other protocol-defined diseases based on imaging at screening period
* Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:

1. safety or well-being of the participant or offspring
2. safety of study staff
3. analysis of results
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Daiichi Sankyo Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

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Texas Oncology, P.A. - Longview

Tyler, Texas, United States

Site Status

Alaska Urological Institute dba Alaska Clinical Research Center

Anchorage, Alaska, United States

Site Status

Arizona Oncology Associates

Tucson, Arizona, United States

Site Status

The Regents of the University of California

Los Angeles, California, United States

Site Status

Sharp Clinical Oncology Research

San Diego, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Sansum Clinic

Santa Barbara, California, United States

Site Status

Innovative Clinical Research Institute, LLC

Whittier, California, United States

Site Status

Sylvester Comprehensive Cancer Center - Deerfield Beach

Boca Raton, Florida, United States

Site Status

Specialist Global Research

Hialeah, Florida, United States

Site Status

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, United States

Site Status

Piedmont Cancer Institute

Atlanta, Georgia, United States

Site Status

Straub Medical Center

Honolulu, Hawaii, United States

Site Status

University of Hawaii

Honolulu, Hawaii, United States

Site Status

Norton Healthcare

Louisville, Kentucky, United States

Site Status

University of Louisville Research Foundation

Louisville, Kentucky, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists

East Setauket, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Aultman Hospital Cancer Center

Canton, Ohio, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

St Francis Hospital

Greenville, South Carolina, United States

Site Status

Accurate Clinical Research

Baytown, Texas, United States

Site Status

Texas Oncology, P.A.

Dallas, Texas, United States

Site Status

Texas Oncology - Memorial City

Houston, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

The Methodist Hospital Research Institute

Houston, Texas, United States

Site Status

The University of Texas Health Science Center at Tyler

Tyler, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Providence Regional Medical Center - Everett

Everett, Washington, United States

Site Status

Imeldaziekenhuis

Bonheiden, , Belgium

Site Status

Grand Hôpital de Charleroi

Charleroi, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

CHU Sart Tilman

Liège, , Belgium

Site Status

AZ Sint-Maarten

Mechelen, , Belgium

Site Status

University of Calgary

Calgary, Alberta, Canada

Site Status

Institut Sainte Catherine

Avignon, , France

Site Status

CHU Besançon - Hôpital Jean Minjoz

Besançon, , France

Site Status

Centre Georges François Leclerc

Dijon, , France

Site Status

CHU Bordeaux - Hôpital Saint André

Gironde, , France

Site Status

CH de la Rochelle - Hopital St Louis

La Rochelle, , France

Site Status

Clinique Victor Hugo - Centre Jean Bernard

Le Mans, , France

Site Status

Hôpital Nord - CHU Marseille

Marseille, , France

Site Status

Institut Régional du Cancer de Montpellier

Montpellier, , France

Site Status

Centre Catherine de Sienne

Nantes, , France

Site Status

Hôpital Saint-Louis - Paris

Paris, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

CRLCC Eugene Marquis

Rennes, , France

Site Status

Hôpital d'Instruction des Armees Begin

Saint-Mandé, , France

Site Status

Centre Paul Strauss

Strasbourg, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Ospedale San Raffaele

Milan, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

IEO Istituto Europeo di Oncologia

Milan, , Italy

Site Status

Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)

Monza, , Italy

Site Status

Ospedale degli Infermi

Rimini, , Italy

Site Status

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Torrette, , Italy

Site Status

NHO Shikoku Cancer Center

Matsuyama, Ehime, Japan

Site Status

Toranomon Hospital

Minatoku, Tokyo-To, Japan

Site Status

Aichi Cancer Center Hospital

Aichi, , Japan

Site Status

National Cancer Center Hospital East

Chiba, , Japan

Site Status

NHO Kyushu Cancer Center

Fukuoka, , Japan

Site Status

Hakuaikai Sagara Hospital

Kagoshima, , Japan

Site Status

Kanagawa Cancer Center

Kanagawa, , Japan

Site Status

Kindai University Hospital

Osaka, , Japan

Site Status

National Cancer Center Hospital

Tokyo, , Japan

Site Status

St. Luke's International Hospital

Tokyo, , Japan

Site Status

Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status

Kyungpook National University Chilgok Hospital

Daegu, , South Korea

Site Status

National Cancer Center

Goyang-si, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital Infanta Cristina

Badajoz, , Spain

Site Status

Hospital Universitari Quiron Dexeus

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

ICO l´Hospitalet - Hospital Duran i Reynals

Barcelona, , Spain

Site Status

Hospital Quiron Barcelona

Barcelona, , Spain

Site Status

MD Anderson Cancer Centre

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Clinico Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Instituto Valenciano de Oncologia IVO

Valencia, , Spain

Site Status

Derriford Hospital

Plymouth, Devon, United Kingdom

Site Status

Queen Mary University of London

London, Greater London, United Kingdom

Site Status

University College London Hospitals

London, Greater London, United Kingdom

Site Status

Western General Hospital

Edinburgh, Lothian Region, United Kingdom

Site Status

Nottingham University Hospitals City Campus

Nottingham, Nottinghamshire, United Kingdom

Site Status

Royal Surrey County Hospital

Guildford, Surrey, United Kingdom

Site Status

Countries

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United States Belgium Canada France Italy Japan South Korea Spain United Kingdom

References

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Dunton K, Vondeling G, Hancock E, Petrou M, Burn O, Paine A. Methods for Estimating Long-Term Outcomes for Trastuzumab Deruxtecan in HER2-Positive Unresectable or Metastatic Breast Cancer After Two or More Anti-HER2 Therapies. Target Oncol. 2022 Nov;17(6):655-663. doi: 10.1007/s11523-022-00923-9. Epub 2022 Nov 7.

Reference Type DERIVED
PMID: 36342619 (View on PubMed)

Rugo HS, Bianchini G, Cortes J, Henning JW, Untch M. Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. ESMO Open. 2022 Aug;7(4):100553. doi: 10.1016/j.esmoop.2022.100553. Epub 2022 Aug 11.

Reference Type DERIVED
PMID: 35964548 (View on PubMed)

Bardia A, Harnden K, Mauro L, Pennisi A, Armitage M, Soliman H. Clinical Practices and Institutional Protocols on Prophylaxis, Monitoring, and Management of Selected Adverse Events Associated with Trastuzumab Deruxtecan. Oncologist. 2022 Aug 5;27(8):637-645. doi: 10.1093/oncolo/oyac107.

Reference Type DERIVED
PMID: 35642907 (View on PubMed)

Modi S. Trastuzumab deruxtecan in previously treated HER2-positive metastatic breast cancer: Plain language summary of the DESTINY-Breast01 study. Future Oncol. 2021 Sep 1;17(26):3415-3423. doi: 10.2217/fon-2021-0427. Epub 2021 Jul 15.

Reference Type DERIVED
PMID: 34263665 (View on PubMed)

Yin O, Iwata H, Lin CC, Tamura K, Watanabe J, Wada R, Kastrissios H, AbuTarif M, Garimella T, Lee C, Zhang L, Shahidi J, LaCreta F. Exposure-Response Relationships in Patients With HER2-Positive Metastatic Breast Cancer and Other Solid Tumors Treated With Trastuzumab Deruxtecan. Clin Pharmacol Ther. 2021 Oct;110(4):986-996. doi: 10.1002/cpt.2291. Epub 2021 Jun 10.

Reference Type DERIVED
PMID: 33999422 (View on PubMed)

Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I; DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):610-621. doi: 10.1056/NEJMoa1914510. Epub 2019 Dec 11.

Reference Type DERIVED
PMID: 31825192 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2016-004986-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

JapicCTI-173693(en)

Identifier Type: REGISTRY

Identifier Source: secondary_id

DESTINY-Breast01

Identifier Type: OTHER

Identifier Source: secondary_id

DS8201-A-U201

Identifier Type: -

Identifier Source: org_study_id

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