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DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03329690
Recruitment Status : Active, not recruiting
First Posted : November 6, 2017
Results First Posted : November 26, 2020
Last Update Posted : November 26, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

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.

Condition or disease Intervention/treatment Phase
Neoplasm, Gastrointestinal Drug: DS-8201a Drug: Physician's Choice Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 233 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Actual Study Start Date : October 12, 2017
Actual Primary Completion Date : November 8, 2019
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Parallel: DS-8201a
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.
Drug: DS-8201a
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.
Other Name: Experimental product

Active Comparator: Parallel: Physician's Choice
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.
Drug: Physician's Choice

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)

Other Name: Standard of Care

Exploratory: Naïve HER2 IHC 2+/ISH-
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.
Drug: DS-8201a
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.
Other Name: Experimental product

Exploratory: Naïve HER2 IHC 1+
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.
Drug: DS-8201a
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.
Other Name: Experimental product




Primary Outcome Measures :
  1. 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) [ Time Frame: Baseline to date of first documented objective response (CR or PR), up to 25 months postdose ]
    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.

  2. 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) [ Time Frame: Baseline to date of first documented objective response, up to 25 months postdose ]
    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 :
  1. Overall Survival Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Intent-to-Treat Analysis Set) [ Time Frame: From the date of randomization to the date of death (due to any cause), up to 25 months postdose ]
    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.

  2. 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) [ Time Frame: From the date of randomization to the first documented disease progression or date of death (whichever occurs first), up to 25 months postdose ]
    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.

  3. 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) [ 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 25 months postdose ]
    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.

  4. 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) [ Time Frame: Baseline to date of first documented objective response (CR, PR, and SD), up to 25 months postdose ]
    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.

  5. 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) [ Time Frame: From randomization to first documented objective response, up to 25 months postdose ]
    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.

  6. Time to Treatment Failure Following Treatment With DS-8201a in Participants With HER2-Expressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (Full Analysis Set) [ Time Frame: From date of randomization to first documentation of PD, death due to any cause, or treatment discontinuation (whichever comes first), up to 25 months postdose ]
    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.

  7. 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) [ Time Frame: From randomization to first documented objective response, up to 25 months postdose ]
    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.

  8. Pharmacokinetic Parameter of Maximum Observed Serum Concentration (Cmax) and Trough Serum Concentration (Ctrough) of DS-8201a, Total Anti-HER2 Antibody, and MAAA-1181 Following Treatment With DS-8201a [ 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) ]
  9. Pharmacokinetic Parameters of Area Under the Concentration Versus-Time Curve of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a [ 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) ]
    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.

  10. Pharmacokinetic Parameter of Time to Maximum Serum Concentration (Tmax) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a [ 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) ]
  11. Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of DS-8201a, Total Anti-HER2 Antibody and MAAA-1181 Following Treatment With DS-8201a [ 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) ]
  12. 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) [ Time Frame: Baseline up to 47 days after last dose, up to 25 months postdose ]
    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.

  13. 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) [ Time Frame: Baseline up to 47 days after last dose, up to 25 months postdose ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has a pathologically documented locally advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction
  2. Progression on and after at least 2 prior regimens
  3. Has an adequate tumor sample
  4. Has measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

Exclusion Criteria:

  1. Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia
  2. Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females
  3. Has a medical history of clinically significant lung disease
  4. Is suspected to have certain other protocol-defined diseases based on imaging at screening period
  5. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03329690


Locations
Show Show 66 study locations
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
AstraZeneca
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Publications of Results:
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Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT03329690    
Other Study ID Numbers: DS8201-A-J202
173727 ( Registry Identifier: JAPIC CTI )
DESTINY-G01 ( Other Identifier: Daiichi Sankyo and AstraZeneca )
First Posted: November 6, 2017    Key Record Dates
Results First Posted: November 26, 2020
Last Update Posted: November 26, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
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.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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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
Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Adenocarcinoma Metastatic
Adenocarcinoma of the Stomach
Adenocarcinoma of the Gastroesophageal Junction
HER2 Overexpression
Adenocarcinoma, Locally Advanced
DESTINY - Gastric 01
Additional relevant MeSH terms:
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Adenocarcinoma
Gastrointestinal Neoplasms
Digestive System Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases