DS-8201a in HER2-positive Gastric Cancer That Cannot Be Surgically Removed or Has Spread (DESTINY-Gastric02)

• ClinicalTrials.gov Identifier: NCT04014075
• Recruitment Status: Active, not recruiting
• First Posted: July 10, 2019
• Results First Posted: January 12, 2022
• Last Update Posted: May 3, 2023
• Sponsor: Daiichi Sankyo, Inc.
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Daiichi Sankyo, Inc.

Tracking Information

• First Submitted Date: July 8, 2019
• First Posted Date: July 10, 2019
• Results First Submitted Date: December 14, 2021
• Results First Posted Date: January 12, 2022
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: November 26, 2019
• Actual Primary Completion Date: November 8, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2023)

• 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 [ Time Frame: Up to 16 months (data cut-off) ]
  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.
• 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 [ Time Frame: Up to 23 months (data cut-off) ]
  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.

Original Primary Outcome Measures (submitted: July 8, 2019)

Objective Response Rate (ORR), Confirmed by Independent Central Review [ Time Frame: within approximately 30 months ]

ORR is defined as the percentage of participants with Best Response of Complete Response (CR) or Partial Response (CR), assessed by Independent Central Review using Response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)

Current Secondary Outcome Measures (submitted: April 27, 2023)

• 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 [ Time Frame: Up to 16 months (data cut-off) ]
  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) Based on Independent Central Review Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma [ Time Frame: Up to 23 months (data cut-off) ]
  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) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma [ Time Frame: Up to 16 months (data cut-off) ]
  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.
• 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 [ Time Frame: Up to 16 months (data cut-off) ]
  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 (ORR) Based on Investigator Assessment Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma [ Time Frame: Up to 23 months (data cut-off) ]
  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.
• Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma [ Time Frame: Up to 16 months (data cut-off) ]
  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) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma [ Time Frame: Up to 23 months (data cut-off) ]
  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.
• Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma [ Time Frame: Up to 16 months (data cut-off) ]
  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) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma [ Time Frame: Up to 23 months (data cut-off) ]
  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.

Original Secondary Outcome Measures (submitted: July 8, 2019)

• Progression-Free Survival (PFS), based on Independent Central Review using RECIST v1.1 [ Time Frame: within approximately 30 months ]
  PFS is defined as the time from enrollment until objective tumor progression or withdrawing from the study for other reasons, whichever occurs first.
• PFS, based on Investigator Assessment [ Time Frame: within approximately 30 months ]
  The time from enrollment until disease progression or withdrawing from the study for other reasons, whichever occurs first, as assessed by the Investigator
• ORR, based on Investigator Assessment [ Time Frame: within approximately 30 months ]
  The percentage of participants with Best Response of Complete Response (CR) or Partial Response (PR), assessed by the Investigator
• Overall Survival (OS) [ Time Frame: within approximately 30 months ]
  Overall survival is defined as the time from enrollment until death from any cause, and is measured in the intent-to-treat population.
• Duration of Response (DoR) [ Time Frame: within approximately 30 months ]
  DoR is defined as the length of time the Best Response of CR or PR continued

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DS-8201a in HER2-positive Gastric Cancer That Cannot Be Surgically Removed or Has Spread (DESTINY-Gastric02)
• Official Title: A Phase 2, Open-label, Single-arm Trial of Trastuzumab Deruxtecan (DS 8201a) in HER2-positive, Unresectable or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma Subjects Who Have Progressed on or After a Trastuzumab-containing Regimen (DESTINY-Gastric02)

Brief Summary

This study will find out if trastuzumab deruxtecan is safe and works for participants with gastric or gastroesophageal junction cancer.

They must have human epidermal growth factor receptor 2 (HER2)-positive gastric or gastro-esophageal junction (GEJ) cancer:

• that cannot be removed surgically
• that has moved to other parts of the body
• that got worse during or after treatment that included trastuzumab

The study will enroll about 80 participants. Sites will be in North America and the European Union.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Adenocarcinoma Gastric Stage IV With Metastases
• Adenocarcinoma - GEJ

Intervention

Drug: Trastuzumab deruxtecan

Antibody component covalently conjugated to a drug component, prepared by dilution based on body weight for intravenous (IV) infusion

Other Name: DS-8201a

Study Arms

Experimental: All participants

Participants who have centrally confirmed HER2-positive gastric or gastro-esophageal junction cancer will be treated with trastuzumab deruxtecan by intravenous (IV) infusion every 3 weeks, until progression of disease or withdrawal from treatment for other reasons.

Intervention: Drug: Trastuzumab deruxtecan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 19, 2021): 79
• Original Estimated Enrollment (submitted: July 8, 2019): 72
• Estimated Study Completion Date: February 2024
• Actual Primary Completion Date: November 8, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men or women ≥18 years old (local regulatory guidelines apply)
• Has pathologically documented HER2-positive gastric or GEJ cancer that is unresectable or metastatic, and that progressed during or after treatment regimen containing trastuzumab
• Has at least one measurable lesion per RECIST v1.1, as confirmed by investigator review
• If of reproductive potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug

Exclusion Criteria:

• Has had anticancer therapy after first-line treatment regimen containing trastuzumab
• Has uncontrolled cardiovascular disease, including any of the following: history of myocardial infarction (MI) within 6 months of first dose or symptomatic congestive heart failure (New York Heart Association Class II to IV), troponin levels consistent with MI as defined according to the manufacturer within 28 days of first dose, or corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (male) based on screening triplicate 12-lead electrocardiogram (ECG)
• Has history of non-infectious interstitial lung disease (ILD)/pneumonitis that required corticosteroid therapy, or current ILD/pneumonitis that cannot be ruled out at screening
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the first dose, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy.
• Has pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART)
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms (Note: participants with clinically inactive brain metastases may be included in the study as well as participants with treated brain metastases who are no longer symptomatic and no longer require treatment with corticosteroids or anticonvulsants.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Italy, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04014075
• Other Study ID Numbers: DS8201-A-U205; 2019-001512-34 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: 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/

• Current Responsible Party: Daiichi Sankyo, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Daiichi Sankyo, Inc.
• Original Study Sponsor: Same as current
• Collaborators: AstraZeneca

Investigators

• Study Director: Global Clinical Leader; Daiichi Sankyo, Inc.

• PRS Account: Daiichi Sankyo, Inc.
• Verification Date: April 2023