Back to resultsDS-8201a in Patients With Cancer That Tests Positive for Human Epidermal Growth Factor Receptor 2 (HER2) Protein
Primary Purpose
Adenocarcinoma, Gastric, Neoplasm, Breast
Status
Completed
Phase
Phase 1
Locations
Taiwan
Study Type
Interventional
Intervention
DS-8201a
Sponsored by
About this trial
This is an interventional treatment trial for Adenocarcinoma, Gastric focused on measuring Stomach cancer, Cancer where the esophagus meets the stomach, Human epidermal growth factor 2, HER2, Breast Cancer, Adenocarcinoma, Gastroesophageal Junction (GEJ), Gastric Cancer, Antibody drug conjugate (ADC), Oncology
Eligibility Criteria
Inclusion Criteria:
- Has a pathologically documented unresectable or metastatic gastric or GEJ adenocarcinoma, or breast cancer, with HER2 expression [immunohistochemistry (IHC) 3+, 2+, or 1+ and/or in situ hybridization (ISH) +] that is refractory to or intolerable with standard treatment, or for which no standard treatment is available
- Has a left ventricular ejection fraction (LVEF) ≥ 50%
- Has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
Exclusion Criteria:
- Has a medical history of myocardial infarction within 6 months before enrollment
- Has a medical history of ventricular arrhythmias, other than rare occasional premature ventricular contractions
- Has uncontrolled or significant cardiovascular disease
Has any other history or condition that might compromise:
- Safety of the participant or offspring
- Safety of study staff
- Analysis of Results
Sites / Locations
- National Taiwan University Hospital
- Taipei Veterans General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
DS-8201a
Arm Description
DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks (Q3W)
Outcomes
Primary Outcome Measures
Treatment-emergent Adverse Events Following Treatment With DS-8201a (Trastuzumab Deruxtecan)
Adverse events (AEs) were to be coded using MedDRA Version 20.1 and assigned severity grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiating the study drug until 47 days after last dose of study drug.
Secondary Outcome Measures
Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Maximum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Maximum concentration (Cmax) of MAAA-1181a was assessed.
Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Area under the serum concentration-time curve during dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody was assessed.
Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Area under the serum concentration-time curve during dosing interval (AUCtau) of MAAA-1181a was assessed.
Best Overall Response By The Investigator's Assessment (Unconfirmed) in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Best overall response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Complete response (CR) was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
Objective Response Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Objective response rate (ORR; defined as participants who achieved CR and PR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
Disease Control Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Disease control rate (DCR; defined as participants who achieved CR, PR, and SD) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions.
Full Information
NCT ID
NCT03368196
First Posted
December 4, 2017
Last Updated
November 2, 2022
Sponsor
Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT03368196
Brief Title
DS-8201a in Patients With Cancer That Tests Positive for Human Epidermal Growth Factor Receptor 2 (HER2) Protein
Official Title
Phase 1, Multicenter, Open-label Study of DS-8201a to Assess Safety and Pharmacokinetics in Subjects With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
April 2, 2018 (Actual)
Primary Completion Date
September 14, 2018 (Actual)
Study Completion Date
September 28, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
HER2-positive cancer is a cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). HER2 promotes the growth of certain cancer cells. This study will test DS-8201a (trastuzumab deruxtecan), a HER2-targeted antibody and topoisomerase I inhibitor conjugate.
The safety and tolerability profile of DS-8201a will be assessed in Chinese patients with certain types of stomach and breast cancer that test positive for HER2. It also will test how DS-8201a moves within the body (pharmacokinetics).
Detailed Description
The expected time from the first subject's enrollment until the last subject's enrollment is approximately 8 months. The screening period is 28 days and each cycle of treatment is 21 days.
The number of treatment cycles is not fixed in this study. Subjects who continue to derive clinical benefit from the study drug in the absence of withdrawal of consent, progressive disease (PD), or unacceptable toxicity may continue the study drug.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma, Gastric, Neoplasm, Breast
Keywords
Stomach cancer, Cancer where the esophagus meets the stomach, Human epidermal growth factor 2, HER2, Breast Cancer, Adenocarcinoma, Gastroesophageal Junction (GEJ), Gastric Cancer, Antibody drug conjugate (ADC), Oncology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DS-8201a
Arm Type
Experimental
Arm Description
DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks (Q3W)
Intervention Type
Drug
Intervention Name(s)
DS-8201a
Intervention Description
An antibody drug conjugate
Primary Outcome Measure Information:
Title
Treatment-emergent Adverse Events Following Treatment With DS-8201a (Trastuzumab Deruxtecan)
Description
Adverse events (AEs) were to be coded using MedDRA Version 20.1 and assigned severity grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiating the study drug until 47 days after last dose of study drug.
Time Frame
Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose
Secondary Outcome Measure Information:
Title
Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Description
Maximum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
Time Frame
Cycles 1 and 3, Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4, 24 hours, 72 hours; Days 8, and 15; Cycles 2, 4, 6 and 8, Day 1: BI and EOI
Title
Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Description
Maximum concentration (Cmax) of MAAA-1181a was assessed.
Time Frame
Cycles 1 and 3, Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4, 24 hours, 72 hours; Days 8, and 15; Cycles 2, 4, 6 and 8, Day 1: BI and EOI
Title
Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Description
Area under the serum concentration-time curve during dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody was assessed.
Time Frame
Cycles 1 and 3, Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4, 24 hours, 72 hours; Days 8, and 15; Cycles 2, 4, 6 and 8, Day 1: BI and EOI
Title
Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Description
Area under the serum concentration-time curve during dosing interval (AUCtau) of MAAA-1181a was assessed.
Time Frame
Cycles 1 and 3, Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4, 24 hours, 72 hours; Days 8, and 15; Cycles 2, 4, 6 and 8, Day 1: BI and EOI
Title
Best Overall Response By The Investigator's Assessment (Unconfirmed) in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Description
Best overall response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Complete response (CR) was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
Time Frame
Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose
Title
Objective Response Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Description
Objective response rate (ORR; defined as participants who achieved CR and PR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
Time Frame
Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose
Title
Disease Control Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Description
Disease control rate (DCR; defined as participants who achieved CR, PR, and SD) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame
Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has a pathologically documented unresectable or metastatic gastric or GEJ adenocarcinoma, or breast cancer, with HER2 expression [immunohistochemistry (IHC) 3+, 2+, or 1+ and/or in situ hybridization (ISH) +] that is refractory to or intolerable with standard treatment, or for which no standard treatment is available
Has a left ventricular ejection fraction (LVEF) ≥ 50%
Has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1
Exclusion Criteria:
Has a medical history of myocardial infarction within 6 months before enrollment
Has a medical history of ventricular arrhythmias, other than rare occasional premature ventricular contractions
Has uncontrolled or significant cardiovascular disease
Has any other history or condition that might compromise:
Safety of the participant or offspring
Safety of study staff
Analysis of Results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Leader
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei
ZIP/Postal Code
112
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
IPD Sharing Time Frame
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
IPD Sharing Access Criteria
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/
Learn more about this trial
DS-8201a in Patients With Cancer That Tests Positive for Human Epidermal Growth Factor Receptor 2 (HER2) Protein
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