Clinical trial NCT03248492: A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)
Official title: A Phase 2, Multicenter, Open-Label Study of DS-8201a, an Anti-HER2-Antibody Drug Conjugate (ADC) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1 (DESTINY-Breast01)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: HER-2 positive breast cancer
Metastatic or Unresectable
Resistant or refractory to T-DM1
DESTINY - Breast 01
Trastuzumab deruxtecan
T-DXd
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
name: Daiichi Sankyo Co., Ltd.
First posted: 2017-08-14
Enrollment: 253
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: HER2-positive patients will be classified into two groups: T-DM1 resistant/refractory (experimental) and T-DM1 intolerant (exploratory only).
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate as Confirmed by Independent Central Review Following Intravenous Administration of 5.4 mg/kg DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
timeFrame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Secondary outcomes:
measure: Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
timeFrame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
measure: Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
timeFrame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
measure: Disease Control Rate and Clinical Benefit Rate as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
timeFrame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
measure: Duration of Response (Complete Response or Partial Response) as Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
timeFrame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
measure: Progression-Free Survival Estimate As Confirmed by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
timeFrame: at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
measure: Percent Change From Baseline in Sum of Diameters Over Time as Determined by Independent Central Review Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)
timeFrame: Baseline up to Week 6, 12, 18, 24, 30, 36 post dose
measure: Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)
timeFrame: Day 0 to Day 47 post last dose
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Urological Institute dba Alaska Clinical Research Center
state: Alaska
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Los Angeles
country: United States
facility: The Regents of the University of California
state: California
city: San Diego
country: United States
facility: Sharp Clinical Oncology Research
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute, LLC
state: California
city: Boca Raton
country: United States
facility: Sylvester Comprehensive Cancer Center - Deerfield Beach
state: Florida
city: Hialeah
country: United States
facility: Specialist Global Research
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health, Inc.
state: Florida
city: Atlanta
country: United States
facility: Piedmont Cancer Institute
state: Georgia
city: Honolulu
country: United States
facility: Straub Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Louisville
country: United States
facility: Norton Healthcare
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Research Foundation
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Canton
country: United States
facility: Aultman Hospital Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: St Francis Hospital
state: South Carolina
city: Baytown
country: United States
facility: Accurate Clinical Research
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Memorial City
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Longview
state: Texas
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Everett
country: United States
facility: Providence Regional Medical Center - Everett
state: Washington
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU Sart Tilman
city: Mechelen
country: Belgium
facility: AZ Sint-Maarten
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besançon
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Gironde
country: France
facility: CHU Bordeaux - Hôpital Saint André
city: La Rochelle
country: France
facility: CH de la Rochelle - Hopital St Louis
city: Le Mans
country: France
facility: Clinique Victor Hugo - Centre Jean Bernard
city: Marseille
country: France
facility: Hôpital Nord - CHU Marseille
city: Montpellier
country: France
facility: Institut Régional du Cancer de Montpellier
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Paris
country: France
facility: Hôpital Saint-Louis - Paris
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rennes
country: France
facility: CRLCC Eugene Marquis
city: Saint-Mandé
country: France
facility: Hôpital d'Instruction des Armees Begin
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)
city: Rimini
country: Italy
facility: Ospedale degli Infermi
city: Torrette
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
city: Matsuyama
country: Japan
facility: NHO Shikoku Cancer Center
state: Ehime-Ken
city: Minato-Ku
country: Japan
facility: Toranomon Hospital
state: Tokyo-To
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Fukuoka
country: Japan
facility: NHO Kyushu Cancer Center
city: Kagoshima
country: Japan
facility: Hakuaikai Sagara Hospital
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: St. Luke's International Hospital
city: Tokyo
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina
city: Barcelona
country: Spain
facility: Hospital Universitari Quiron Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: ICO l´Hospitalet - Hospital Duran i Reynals
city: Barcelona
country: Spain
facility: Hospital Quiron Barcelona
city: Madrid
country: Spain
facility: MD Anderson Cancer Centre
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia IVO
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: London
country: United Kingdom
facility: Queen Mary University of London
state: Greater London
city: London
country: United Kingdom
facility: University College London Hospitals
state: Greater London
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Lothian Region
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals City Campus
state: Nottinghamshire
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
state: Surrey
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.