Clinical Trial Results:
A PHASE 2, OPEN-LABEL, SINGLE-ARM TRIAL OF TRASTUZUMAB DERUXTECAN (DS-8201A) IN HER2-POSITIVE, UNRESECTABLE OR METASTATIC GASTRIC OR GASTROESOPHAGEAL JUNCTION (GEJ) ADENOCARCINOMA SUBJECTS WHO HAVE PROGRESSED ON OR AFTER A TRASTUZUMAB-CONTAINING REGIMEN
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Summary
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EudraCT number |
2019-001512-34 |
Trial protocol |
ES BE IT |
Global end of trial date |
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Results information
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Results version number |
v2(current) |
This version publication date |
24 Feb 2023
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First version publication date |
01 Mar 2022
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
DS8201-A-U205
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04014075 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Daiichi Sankyo Inc.
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Sponsor organisation address |
211 Mt. Airy Rd., Basking Ridge, United States, 07920
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Public contact |
Global Clinical Director, Daiichi Sankyo Inc., +1 908-992-6400, CTRinfo@dsi.com
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Scientific contact |
Global Clinical Director, Daiichi Sankyo Inc., +1 908-992-6400, CTRinfo@dsi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
09 Apr 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Apr 2021
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Global end of trial reached? |
No
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General information about the trial
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Main objective of the trial |
To investigate the efficacy of Trastuzumab Deruxtecan (DS-8201a) based on objective response rate (ORR) by independent central review based on Response Evaluation Criteria in Solid Tumors (RECIST), version (v)1.1
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Protection of trial subjects |
The study protocol, amendments, the informed consent form(s) (ICF[s]), and information sheets were approved by the appropriate and applicable Independent Ethics Committees (IECs) or Institutional
Review Boards (IRBs). The study was conducted in compliance with the protocol, the ethical principles that have their origin in the Declaration of Helsinki, the International Council for Harmonisation (ICH)
consolidated Guideline E6 for Good Clinical Practice (GCP) (CPMP/ICH/135/95), and applicable regulatory requirement(s).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Nov 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
European Union: 45
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Country: Number of subjects enrolled |
United States: 34
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Worldwide total number of subjects |
79
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
46
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From 65 to 84 years |
33
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 79 participants who met all inclusion criteria and no exclusion criteria were enrolled and treated at clinic centers in United States, Spain, Italy, United Kingdom, and Belgium. Primary results reported is from baseline up to data cut-off date of 08 Nov 2021. | ||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 89 participants were screened and 10 participants failed screening. The results presented are based on primary analysis up to 23 months. Data collection is still on-going and additional results will be provided after study completion. | ||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
Blinding implementation details |
This was an open-label study.
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Arms
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Arm title
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Trastuzumab Deruxtecan | ||||||||||||||||||||||
Arm description |
Participants who have centrally confirmed HER2-positive gastric or gastro-esophageal junction cancer received an intravenous (IV) infusion 6.4 mg/kg dose of trastuzumab deruxtecan every 3 weeks, until progression of disease or withdrawal from treatment for other reasons. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
DS-8201a
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Investigational medicinal product code |
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Other name |
Trastuzumab deruxtecan
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion.
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Baseline characteristics reporting groups
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Reporting group title |
Overall
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Reporting group description |
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End points reporting groups
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Reporting group title |
Trastuzumab Deruxtecan
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Reporting group description |
Participants who have centrally confirmed HER2-positive gastric or gastro-esophageal junction cancer received an intravenous (IV) infusion 6.4 mg/kg dose of trastuzumab deruxtecan every 3 weeks, until progression of disease or withdrawal from treatment for other reasons. | ||
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End point title |
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma [1] | ||||||||||||
End point description |
The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on 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. Confirmed ORR based on ICR is reported. Objective response rate was assessed in the Full Analysis Set at data cut-off dates (09 April 2021 and 08 Nov 2021).
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End point type |
Primary
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End point timeframe |
Up to 23 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Upper CI was not estimable. Curve representing the upper confidence limits for the survivor function was above 0.5. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Progression-Free Survival (PFS) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | ||||||||||||
End point description |
Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off dates (09 April 2021 and 08 Nov 2021).
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End point type |
Secondary
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End point timeframe |
Up to 23 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Progression-Free Survival (PFS) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | ||||||||
End point description |
Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 09 April 2021.
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End point type |
Secondary
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End point timeframe |
Up to 16 months (data cut-off)
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| No statistical analyses for this end point | |||||||||
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End point title |
Objective Response Rate (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | ||||||||||||
End point description |
The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment based on 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. Confirmed ORR based on investigator assessment is reported. Objective response rate was assessed in the Full Analysis Set at data cut-off dates (09 April 2021 and 08 Nov 2021).
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End point type |
Secondary
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End point timeframe |
Up to 23 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | ||||||||||||
End point description |
Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause. Overall survival (OS) was assessed in the Full Analysis Set at data cut-off dates (09 April 2021 and 08 Nov 2021).
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End point type |
Secondary
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End point timeframe |
Up to 23 months
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| Notes [2] - For 16 months, 99.9=NA, median and upper limit CI not estimable due to insufficient number of events |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma | ||||||||||||
End point description |
Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR based on independent central review. Duration of Response (DOR) was assessed in the Full Analysis Set at data cut-off dates (09 April 2021 and 08 Nov 2021).
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End point type |
Secondary
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End point timeframe |
Up to 23 months
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| Notes [3] - 99.9=NA, upper limit CI was not estimable. Curve for survivor function was above 0.5. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up 23 months.
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Adverse event reporting additional description |
A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
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Reporting groups
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Reporting group title |
Trastuzumab Deruxtecan
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Reporting group description |
Participants who have centrally confirmed HER2-positive gastric or gastro-esophageal junction cancer received an intravenous (IV) infusion 6.4 mg/kg dose of trastuzumab deruxtecan every 3 weeks, until progression of disease or withdrawal from treatment for other reasons. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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17 Sep 2020 |
Updated endpoints to provide clarification, updated study schema, updated inclusion and exclusion criteria, updated guidelines for dose modifications, updated concomitant medications, treatments, and procedures, updated treatment period section, updated PK assessments due to COVID-19 infection, updated PK, biomarker, and AE analyses to provide clarification, added instructions related to COVID-19 |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
