Back to resultsDS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]
Primary Purpose
Neoplasm, Gastrointestinal
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
DS-8201a
Physician's Choice
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasm, Gastrointestinal focused on measuring Adenocarcinoma Metastatic, Adenocarcinoma of the Stomach, Adenocarcinoma of the Gastroesophageal Junction, HER2 Overexpression, Adenocarcinoma, Locally Advanced, DESTINY - Gastric 01
Eligibility Criteria
Inclusion Criteria:
- Has a pathologically documented locally advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction
- Progression on and after at least 2 prior regimens
- Has an adequate tumor sample
- Has measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
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 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:
- safety or well-being of the participant or offspring
- safety of study staff
- analysis of results
Sites / Locations
- Aichi Cancer Center Hospital
- Hirosaki University Hospital
- National Cancer Center Hospital East
- National Hospital Organization Shikoku Cancer Center
- Japan Community Health Care Organization Kyushu Hospital
- Gunma Prefectural Cancer Center
- Kure Medical Center
- Hokkaido University Hospital
- Hyogo Cancer Center
- Kansai Rosai Hospital
- Kobe City Medical Center General Hospital
- Ibaraki Prefectural Central Hospital
- Kanazawa University Hospital
- Iwate Medical University Hospital
- Kagawa University Hospital
- St. Marianna University School of Medicine Hospital
- The Kitasato Institute Kitasato University Hospital
- Yokohama City University Medical Center
- Kanagawa Cancer Center
- Japanese Red Cross Kyoto Daini Hospital
- Miyagi Cancer Center
- Osaki Citizen Hospital
- Osaka University Hospital
- Toyonaka Municipal Hospital
- Tochigi Cancer Center
- Tokyo Metropolitan Komagome Hospital
- National Cancer Center Hospital
- The Cancer Institute Hospital of Japanese Foundation for Cancer Research
- Showa University Koto Toyosu Hospital
- Toranomon Hospital
- Chiba Cancer Center
- Fukui Prefectural Hospital
- National Hospital Organization Kyushu Cancer Center
- Kyushu University Hospital
- Gifu University Hospital
- Hiroshima City Asa Citizens Hospital
- Hiroshima Prefectural Hospital
- Kochi Health Sciences Center
- Niigata Cancer Center Hospital
- Okayama University Hospital
- Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
- Osaka International Cancer Institute
- Osaka General Medical Center
- Kindai University Hospital
- Saitama Cancer Center
- Shizuoka Cancer Center
- Shizuoka General Hospital
- Keio University Hospital
- Chungbuk National University Hospital
- National Cancer Center
- Inje University Haeundae Paik Hospital
- Dong-A University Hospital
- Kyungpook National University Chilgok Hospital
- Chonnam National University Hwasun Hospital
- Gachon University Gil Medical Center
- Chonbuk National University Hospital
- Seoul National University Bundang Hospital
- Korea University Anam Hospital
- Seoul National University Hospital
- Yonsei Cancer Center, Severance Hospital, Yonsei University Health System
- Asan Medical Center
- Gangnam Severance Hospital
- Samsung Medical Center
- The Catholic University of Korea, Seoul St. Mary's Hospital
- Chung-Ang University Hospital
- Korea University Guro Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Other
Other
Arm Label
Parallel: DS-8201a
Parallel: Physician's Choice
Exploratory: Naïve HER2 IHC 2+/ISH-
Exploratory: Naïve HER2 IHC 1+
Arm Description
Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive DS-8201a once every 3 weeks.
Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive monotherapy prescribed by the physician before enrollment.
A maximum of 20 non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma will receive DS-8201a once every three weeks.
A maximum of 20 non-randomized patients with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma will receive DS-8201a once every 3 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by independent central imaging review (ICR) 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. Unconfirmed ORR (not confirmed by ICR) and confirmed ORR (confirmed by ICR) are reported.
Percentage of Participants With Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by independent central imaging review (ICR) based on 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 progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Unconfirmed BOR (not confirmed by ICR) and confirmed BOR (confirmed by ICR) are reported.
Secondary Outcome Measures
Overall Survival Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Duration of survival follow-up (months) was defined as the date of last contact - date of randomization/ registration + 1.Overall Survival (OS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the date of death due to any cause.
Progression-Free Survival Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Progression-free survival (PFS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.
Duration of Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)
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 was measured for responding subjects (PR or CR) only.
Disease Control Rate With and Without Confirmation by Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per RECIST v1.1, 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 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 and Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Independent Central Review (ICR) based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on 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 (at least a 20% increase in the sum of diameters of target lesions). Confirmed ORR and BOR (confirmed by ICR) are reported.
Time to Treatment Failure Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)
Time to treatment failure (TTF) was defined as the time from the date of randomization (the date of the registration for Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD), death due to any cause, or treatment discontinuation.
Objective Response Rate and Best Overall Response Based on Investigator Assessment Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Response Evaluable Set)
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on 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 (at least a 20% increase in the sum of diameters of target lesions). Unconfirmed ORR and BOR (not confirmed by Investigator) and confirmed ORR and BOR (confirmed by Investigator) are reported.
Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of MAAA-1181 Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of MAAA-1181 Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Pharmacokinetic Parameter of Time to Maximum Serum Concentration (Tmax) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The time to maximum serum concentration (Tmax) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Terminal elimination half-life (t1/2) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. (Safety Analysis Set)
A treatment-emergent adverse event (TEAE) is defined as an adverse event 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. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs.
Summary of Most Common Treatment-Emergent Adverse Events (TEAEs) ≥20% of Any Grade by Preferred Term Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Safety Analysis Set)
A treatment-emergent adverse event (TEAE) is defined as an adverse event 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.
Full Information
NCT ID
NCT03329690
First Posted
October 30, 2017
Last Updated
March 17, 2022
Sponsor
Daiichi Sankyo Co., Ltd.
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT03329690
Brief Title
DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]
Official Title
A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
November 2, 2017 (Actual)
Primary Completion Date
November 8, 2019 (Actual)
Study Completion Date
December 11, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo Co., Ltd.
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
Brief Summary
The primary purpose of this trial is to compare the efficacy and safety of DS-8201a and physician's choice treatment in HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma patients who have progressed on two prior treatment regimens including fluoropyrimidine agent, platinum agent, and trastuzumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasm, Gastrointestinal
Keywords
Adenocarcinoma Metastatic, Adenocarcinoma of the Stomach, Adenocarcinoma of the Gastroesophageal Junction, HER2 Overexpression, Adenocarcinoma, Locally Advanced, DESTINY - Gastric 01
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Two randomized investigative arms will run in parallel (DS-8201a and Physician's Choice), with participants who have disease progression after two previous regimens.
Two non-randomized exploratory arms will run with HER2 treatment-naive participants.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
233 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Parallel: DS-8201a
Arm Type
Experimental
Arm Description
Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive DS-8201a once every 3 weeks.
Arm Title
Parallel: Physician's Choice
Arm Type
Active Comparator
Arm Description
Participants with HER2-overexpressing (IHC 3+ or IHC 2+/ISH+) advanced gastric or gastroesophageal junction adenocarcinoma, whose disease has progressed on two prior regimens, will receive monotherapy prescribed by the physician before enrollment.
Arm Title
Exploratory: Naïve HER2 IHC 2+/ISH-
Arm Type
Other
Arm Description
A maximum of 20 non-randomized participants with HER2 IHC 2+/ISH- advanced gastric or gastroesophageal junction adenocarcinoma will receive DS-8201a once every three weeks.
Arm Title
Exploratory: Naïve HER2 IHC 1+
Arm Type
Other
Arm Description
A maximum of 20 non-randomized patients with HER2 IHC 1+ advanced gastric or gastroesophageal junction adenocarcinoma will receive DS-8201a once every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
DS-8201a
Other Intervention Name(s)
Experimental product
Intervention Description
DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration.
Intervention Type
Drug
Intervention Name(s)
Physician's Choice
Other Intervention Name(s)
Standard of Care
Intervention Description
Either:
Irinotecan monotherapy (Starting dosage and usage is 150 mg/m2 biweekly, with dose reduction permitted)
Paclitaxel monotherapy (Starting dosage and usage is 80 mg/m2 weekly, with dose reduction permitted)
Primary Outcome Measure Information:
Title
Percentage of Participants With Objective Response Rate Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Description
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by independent central imaging review (ICR) 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. Unconfirmed ORR (not confirmed by ICR) and confirmed ORR (confirmed by ICR) are reported.
Time Frame
Baseline to date of first documented objective response (CR or PR), up to 36 months postdose
Title
Percentage of Participants With Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Description
The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by independent central imaging review (ICR) based on 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 progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Unconfirmed BOR (not confirmed by ICR) and confirmed BOR (confirmed by ICR) are reported.
Time Frame
Baseline to date of first documented objective response, up to 36 months postdose
Secondary Outcome Measure Information:
Title
Overall Survival Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Description
Duration of survival follow-up (months) was defined as the date of last contact - date of randomization/ registration + 1.Overall Survival (OS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the date of death due to any cause.
Time Frame
From the date of randomization to the date of death (due to any cause), up to 36 months postdose
Title
Progression-Free Survival Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Description
Progression-free survival (PFS) was defined as the time from the date of randomization (the date of the registration for the Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame
From the date of randomization to the first documented disease progression or date of death (whichever occurs first), up to 36 months postdose
Title
Duration of Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)
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 was measured for responding subjects (PR or CR) only.
Time Frame
From the date of first objective response (CR or PR) to the date of first documentation of PD or death (whichever occurs first), up to 36 months postdose
Title
Disease Control Rate With and Without Confirmation by Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Description
Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per RECIST v1.1, 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 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 to date of first documented objective response (CR, PR, and SD), up to 36 months postdose
Title
Objective Response Rate and Best Overall Response Based on Independent Central Review Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set)
Description
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Independent Central Review (ICR) based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on 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 (at least a 20% increase in the sum of diameters of target lesions). Confirmed ORR and BOR (confirmed by ICR) are reported.
Time Frame
From randomization to first documented objective response, up to 36 months postdose
Title
Time to Treatment Failure Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set)
Description
Time to treatment failure (TTF) was defined as the time from the date of randomization (the date of the registration for Exploratory Cohorts) to the earliest date of the first objective documentation of progressive disease (PD), death due to any cause, or treatment discontinuation.
Time Frame
From date of randomization to first documentation of PD, death due to any cause, or treatment discontinuation (whichever comes first), up to 36 months postdose
Title
Objective Response Rate and Best Overall Response Based on Investigator Assessment Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Response Evaluable Set)
Description
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator based on RECIST version 1.1. The best overall response is the best overall response (BOR) recorded from the start of the study treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) as assessed by Investigator based on 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 (at least a 20% increase in the sum of diameters of target lesions). Unconfirmed ORR and BOR (not confirmed by Investigator) and confirmed ORR and BOR (confirmed by Investigator) are reported.
Time Frame
From randomization to first documented objective response, up to 36 months postdose
Title
Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a
Description
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
Time Frame
Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Title
Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of MAAA-1181 Following Treatment With DS-8201a
Description
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The maximum serum concentration (Cmax) and the trough serum concentration (Ctrough) of DS-8201a were assessed. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Time Frame
Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Title
Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a and Total Anti-HER2 Antibody Following Treatment With DS-8201a
Description
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for DS-8201a and total anti-HER2 antibody were estimated in each participant using standard noncompartmental methods.
Time Frame
Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Title
Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of MAAA-1181 Following Treatment With DS-8201a
Description
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Area under the concentration versus time curve (AUC) from Time 0 to the Last Quantifiable Concentration (AUClast) and Area Under the Concentration versus-Time Curve up to 21 days (AUC21d) are reported. These serum PK parameters for MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Time Frame
Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Title
Pharmacokinetic Parameter of Time to Maximum Serum Concentration (Tmax) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a
Description
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. The time to maximum serum concentration (Tmax) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Time Frame
Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Title
Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a
Description
Blood samples for DS-8201a pharmacokinetic (PK) analysis were obtained at the specified timepoints. Terminal elimination half-life (t1/2) of DS-8201a was assessed. This serum PK parameter for DS-8201a, total anti-HER2 antibody, and MAAA-1181a were estimated in each participant using standard noncompartmental methods.
Time Frame
Cycle 1 and 3, Day 1: predose, 4 hours (h), 7h postdose; Day 8, Day 15, and Day 22 postdose; Cycle 2, Day 1 and Day 22 postdose; Cycle 4, 6, and 8, Day 1 postdose (each cycle is 21 days)
Title
Overall Summary of Treatment-emergent Adverse Events (TEAEs) Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. (Safety Analysis Set)
Description
A treatment-emergent adverse event (TEAE) is defined as an adverse event 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. Serious adverse events (SAEs) with an onset or worsening 48 days or more after the last dose of study drug, if considered related to the study treatment, are also TEAEs.
Time Frame
Baseline up to 47 days after last dose, up to 36 months postdose
Title
Summary of Most Common Treatment-Emergent Adverse Events (TEAEs) ≥20% of Any Grade by Preferred Term Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Safety Analysis Set)
Description
A treatment-emergent adverse event (TEAE) is defined as an adverse event 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.
Time Frame
Baseline up to 47 days after last dose, up to 36 months postdose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has a pathologically documented locally advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction
Progression on and after at least 2 prior regimens
Has an adequate tumor sample
Has measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
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 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:
safety or well-being 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
Aichi Cancer Center Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
Hirosaki University Hospital
City
Hirosaki
State/Province
Aomori
ZIP/Postal Code
036-8563
Country
Japan
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
National Hospital Organization Shikoku Cancer Center
City
Matsuyama
State/Province
Ehime
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
Japan Community Health Care Organization Kyushu Hospital
City
Kitakyushu
State/Province
Fukuoka
ZIP/Postal Code
806-8501
Country
Japan
Facility Name
Gunma Prefectural Cancer Center
City
Ōta
State/Province
Gunma
ZIP/Postal Code
373-8550
Country
Japan
Facility Name
Kure Medical Center
City
Kure
State/Province
Hiroshima
ZIP/Postal Code
737-0023
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Hyogo Cancer Center
City
Akashi
State/Province
Hyogo
ZIP/Postal Code
673-8558
Country
Japan
Facility Name
Kansai Rosai Hospital
City
Amagasaki
State/Province
Hyogo
ZIP/Postal Code
660-8511
Country
Japan
Facility Name
Kobe City Medical Center General Hospital
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Ibaraki Prefectural Central Hospital
City
Kasama
State/Province
Ibaraki
ZIP/Postal Code
309-1793
Country
Japan
Facility Name
Kanazawa University Hospital
City
Kanazawa
State/Province
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Iwate Medical University Hospital
City
Shiwa-gun
State/Province
Iwate
ZIP/Postal Code
028-3695
Country
Japan
Facility Name
Kagawa University Hospital
City
Kita
State/Province
Kagawa
ZIP/Postal Code
761-0793
Country
Japan
Facility Name
St. Marianna University School of Medicine Hospital
City
Kawasaki
State/Province
Kanagawa
ZIP/Postal Code
216-8511
Country
Japan
Facility Name
The Kitasato Institute Kitasato University Hospital
City
Sagamihara
State/Province
Kanagawa
ZIP/Postal Code
252-0375
Country
Japan
Facility Name
Yokohama City University Medical Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
232-0024
Country
Japan
Facility Name
Kanagawa Cancer Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
241-8515
Country
Japan
Facility Name
Japanese Red Cross Kyoto Daini Hospital
City
Kamigyō-ku
State/Province
Kyoto
ZIP/Postal Code
602-8026
Country
Japan
Facility Name
Miyagi Cancer Center
City
Natori
State/Province
Miyagi
ZIP/Postal Code
981-1293
Country
Japan
Facility Name
Osaki Citizen Hospital
City
Osaki
State/Province
Miyagi
ZIP/Postal Code
989-6183
Country
Japan
Facility Name
Osaka University Hospital
City
Suita
State/Province
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Toyonaka Municipal Hospital
City
Toyonaka
State/Province
Osaka
ZIP/Postal Code
560-8565
Country
Japan
Facility Name
Tochigi Cancer Center
City
Utsunomiya
State/Province
Tochigi
ZIP/Postal Code
320-0834
Country
Japan
Facility Name
Tokyo Metropolitan Komagome Hospital
City
Bunkyō-Ku
State/Province
Tokyo
ZIP/Postal Code
113-8677
Country
Japan
Facility Name
National Cancer Center Hospital
City
Chuo Ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
City
Koto-Ku
State/Province
Tokyo
ZIP/Postal Code
135-8550
Country
Japan
Facility Name
Showa University Koto Toyosu Hospital
City
Koto-Ku
State/Province
Tokyo
ZIP/Postal Code
135-8577
Country
Japan
Facility Name
Toranomon Hospital
City
Minato-Ku
State/Province
Tokyo
ZIP/Postal Code
105-8470
Country
Japan
Facility Name
Chiba Cancer Center
City
Chiba
ZIP/Postal Code
260-8717
Country
Japan
Facility Name
Fukui Prefectural Hospital
City
Fukui
ZIP/Postal Code
910-8526
Country
Japan
Facility Name
National Hospital Organization Kyushu Cancer Center
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Kyushu University Hospital
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Gifu University Hospital
City
Gifu
ZIP/Postal Code
501-1194
Country
Japan
Facility Name
Hiroshima City Asa Citizens Hospital
City
Hiroshima
ZIP/Postal Code
731-0293
Country
Japan
Facility Name
Hiroshima Prefectural Hospital
City
Hiroshima
ZIP/Postal Code
734-8530
Country
Japan
Facility Name
Kochi Health Sciences Center
City
Kochi
ZIP/Postal Code
781-8555
Country
Japan
Facility Name
Niigata Cancer Center Hospital
City
Niigata
ZIP/Postal Code
951-8566
Country
Japan
Facility Name
Okayama University Hospital
City
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
City
Osaka
ZIP/Postal Code
534-0021
Country
Japan
Facility Name
Osaka International Cancer Institute
City
Osaka
ZIP/Postal Code
541-8567
Country
Japan
Facility Name
Osaka General Medical Center
City
Osaka
ZIP/Postal Code
558-8558
Country
Japan
Facility Name
Kindai University Hospital
City
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Facility Name
Saitama Cancer Center
City
Saitama
ZIP/Postal Code
362-0806
Country
Japan
Facility Name
Shizuoka Cancer Center
City
Shizuoka
ZIP/Postal Code
411-8777
Country
Japan
Facility Name
Shizuoka General Hospital
City
Shizuoka
ZIP/Postal Code
420-8527
Country
Japan
Facility Name
Keio University Hospital
City
Tokyo
ZIP/Postal Code
160-8582
Country
Japan
Facility Name
Chungbuk National University Hospital
City
Cheongju-si
State/Province
Chungcheongbuk-do
ZIP/Postal Code
28644
Country
Korea, Republic of
Facility Name
National Cancer Center
City
Ilsan
State/Province
Gyeonggi-do
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Inje University Haeundae Paik Hospital
City
Busan
ZIP/Postal Code
48108
Country
Korea, Republic of
Facility Name
Dong-A University Hospital
City
Busan
ZIP/Postal Code
49201
Country
Korea, Republic of
Facility Name
Kyungpook National University Chilgok Hospital
City
Daegu
ZIP/Postal Code
41404
Country
Korea, Republic of
Facility Name
Chonnam National University Hwasun Hospital
City
Gwangju
ZIP/Postal Code
58128
Country
Korea, Republic of
Facility Name
Gachon University Gil Medical Center
City
Incheon
ZIP/Postal Code
21565
Country
Korea, Republic of
Facility Name
Chonbuk National University Hospital
City
Jeonju
ZIP/Postal Code
54907
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seongnam
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
Korea University Anam Hospital
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Yonsei Cancer Center, Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Gangnam Severance Hospital
City
Seoul
ZIP/Postal Code
06273
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
The Catholic University of Korea, Seoul St. Mary's Hospital
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Chung-Ang University Hospital
City
Seoul
ZIP/Postal Code
06973
Country
Korea, Republic of
Facility Name
Korea University Guro Hospital
City
Seoul
ZIP/Postal Code
08308
Country
Korea, Republic of
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/
Citations:
PubMed Identifier
32469182
Citation
Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. doi: 10.1056/NEJMoa2004413. Epub 2020 May 29.
Results Reference
result
PubMed Identifier
36379002
Citation
Yamaguchi K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Shimoyama T, Lee KW, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Shitara K. Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. J Clin Oncol. 2023 Feb 1;41(4):816-825. doi: 10.1200/JCO.22.00575. Epub 2022 Nov 15.
Results Reference
derived
Learn more about this trial
DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]
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