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

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03248492
• Other study ID #: DS8201-A-U201
• Secondary ID: 2016-004986-18Ja
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 25, 2017
• Est. completion date: May 31, 2024

Study information

• Verified date: November 2023
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 253
• Est. completion date: May 31, 2024
• Est. primary completion date: March 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Belgium	Imeldaziekenhuis	Bonheiden
Belgium	Grand Hôpital de Charleroi	Charleroi
Belgium	UZ Leuven	Leuven
Belgium	CHU Sart Tilman	Liège
Belgium	AZ Sint-Maarten	Mechelen
Canada	University of Calgary	Calgary	Alberta
France	Institut Sainte Catherine	Avignon
France	CHU Besançon - Hôpital Jean Minjoz	Besançon
France	Centre Georges François Leclerc	Dijon
France	CHU Bordeaux - Hôpital Saint André	Gironde
France	CH de la Rochelle - Hopital St Louis	La Rochelle
France	Clinique Victor Hugo - Centre Jean Bernard	Le Mans
France	Hôpital Nord - CHU Marseille	Marseille
France	Institut Régional du Cancer de Montpellier	Montpellier
France	Centre Catherine de Sienne	Nantes
France	Hôpital Saint-Louis - Paris	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	CRLCC Eugene Marquis	Rennes
France	Hôpital d'Instruction des Armees Begin	Saint-Mandé
France	Centre Paul Strauss	Strasbourg
France	Institut Gustave Roussy	Villejuif
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)	Monza
Italy	Ospedale degli Infermi	Rimini
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona	Torrette
Japan	Aichi Cancer Center Hospital	Aichi
Japan	National Cancer Center Hospital East	Chiba
Japan	NHO Kyushu Cancer Center	Fukuoka
Japan	Hakuaikai Sagara Hospital	Kagoshima
Japan	Kanagawa Cancer Center	Kanagawa
Japan	NHO Shikoku Cancer Center	Matsuyama	Ehime-Ken
Japan	Toranomon Hospital	Minato-Ku	Tokyo-To
Japan	Kindai University Hospital	Osaka
Japan	Cancer Institute Hospital of JFCR	Tokyo
Japan	National Cancer Center Hospital	Tokyo
Japan	St. Luke's International Hospital	Tokyo
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Spain	Hospital Infanta Cristina	Badajoz
Spain	Hospital Quiron Barcelona	Barcelona
Spain	Hospital Universitari Quiron Dexeus	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	ICO l´Hospitalet - Hospital Duran i Reynals	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	MD Anderson Cancer Centre	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Instituto Valenciano de Oncologia IVO	Valencia
United Kingdom	Western General Hospital	Edinburgh	Lothian Region
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	Queen Mary University of London	London	Greater London
United Kingdom	University College London Hospitals	London	Greater London
United Kingdom	Nottingham University Hospitals City Campus	Nottingham	Nottinghamshire
United Kingdom	Derriford Hospital	Plymouth	Devon
United States	Alaska Urological Institute dba Alaska Clinical Research Center	Anchorage	Alaska
United States	Piedmont Cancer Institute	Atlanta	Georgia
United States	Accurate Clinical Research	Baytown	Texas
United States	Sylvester Comprehensive Cancer Center - Deerfield Beach	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Aultman Hospital Cancer Center	Canton	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	North Shore Hematology Oncology Associates PC DBA NY Cancer and Blood Specialists	East Setauket	New York
United States	Providence Regional Medical Center - Everett	Everett	Washington
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	St Francis Hospital	Greenville	South Carolina
United States	Specialist Global Research	Hialeah	Florida
United States	Straub Medical Center	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	MD Anderson Cancer Center	Houston	Texas
United States	Texas Oncology - Memorial City	Houston	Texas
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	The Regents of the University of California	Los Angeles	California
United States	Norton Healthcare	Louisville	Kentucky
United States	University of Louisville Research Foundation	Louisville	Kentucky
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Sharp Clinical Oncology Research	San Diego	California
United States	University of California San Francisco	San Francisco	California
United States	Sansum Clinic	Santa Barbara	California
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Texas Oncology, P.A. - Longview	Tyler	Texas
United States	The University of Texas Health Science Center at Tyler	Tyler	Texas
United States	Innovative Clinical Research Institute, LLC	Whittier	California

Sponsors (3)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.	AstraZeneca, Daiichi Sankyo Co., Ltd.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Italy,  Japan,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	The number of participants with objective response was assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment, by independent central imaging facility review based on RECIST version 1.1.	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Secondary	Objective Response Rate as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)	The number of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through discontinuation of treatment. Investigator-assessed objective response rate (ORR) was defined as the proportion of participants who achieved a best overall response of complete response or partial response based on local radiologists/investigators' tumor assessments.	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Secondary	Best Overall Tumor Response as Confirmed By the Investigator Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Enrolled Analysis Set)	Best overall tumor response was defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator based on RECIST v1.1. Participants who were non-evaluable (NE) are also reported.	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Secondary	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)	Number of participants with controlled disease and who received clinical benefit from treatment as assessed by independent central review. DCR was defined as the proportion of participants who achieved a best overall response of complete response, partial response, or stable disease. CBR was defined as the proportion of participants who achieved a best overall response of complete response or partial response or more than 6 months of stable disease.	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Secondary	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)	The estimated duration of confirmed response (complete response [CR] or partial response [PR]) was assessed by independent central review. Duration of response was defined as the time interval between the date of first documentation of objective response (CR or PR) and the date of the first objective documentation of disease progression or death due to any cause.	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Secondary	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)	The point estimate of progression-free survival (PFS) is reported. PFS was defined as the time interval between the date of randomization/registration and the first documentation of disease progression or death due to any cause.	at least 6 months after last participant enrolled received first dose up to 19 months (data cut off)
Secondary	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)	Best percent change in sum of diameters of measurable tumors was based on RECIST 1.1. The best percent change was defined as the percent change in the smallest sum of diameters from all post-baseline tumor assessments, taking as reference the baseline sum of diameters.	Baseline up to Week 6, 12, 18, 24, 30, 36 post dose
Secondary	Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Intravenous Administration of DS-8201a in Participants With Metastatic Breast Cancer (Safety Analysis Set)	TEAEs were assessed by severity and seriousness according to unique criteria. Severity described the intensity of an event and was graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Serious TEAEs were defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires inpatient hospitalization, or causes prolongation of existing hospitalization.	Day 0 to Day 47 post last dose