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

Adenocarcinoma - GEJ Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04014075
• Other study ID #: DS8201-A-U205
• Secondary ID: 2019-001512-34
• Status: Completed
• Phase: Phase 2
• Start date: November 26, 2019
• Est. completion date: February 13, 2024

Study information

• Verified date: April 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: February 13, 2024
• Est. primary completion date: November 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma - GEJ
• Adenocarcinoma Gastric Stage IV With Metastases

Intervention

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

Locations

Country	Name	City	State
Belgium	UCL St-Luc	Brussels
Belgium	Hopital de Jolimont	Haine-Saint-Paul
Belgium	UZ Leuven	Leuven
Italy	Asst Grande Ospedale Metropolitano Niguarda	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Azienda Ospedaliero Universitaria di Modena Policlinico	Modena
Italy	Oncology Institute Veneto IOVIRCCS	Padua
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Institut Catalan de Oncologia Hospital Duran i Reynals	Barcelona
Spain	Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO)	Barcelona
Spain	Hospital la Paz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Biomedical Research Institute Hospital de Valencia	Valencia
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	The Royal Marsden Hospital	Sutton
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Beth Israel Deaconess Medical Center (BIDMC)	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital (MGH)	Boston	Massachusetts
United States	University of Chicago Medical Center UCMC Duchossois Center for Advanced Medicine DCAM	Chicago	Illinois
United States	City of Hope Medical Center	Duarte	California
United States	Hartford Hospital	Hartford	Connecticut
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Kansas University Cancer Center	Kansas City	Kansas
United States	Northwell Health Cancer Institute	Lake Success	New York
United States	USC Norris Comprehensive Cancer Center Hospital	Los Angeles	California
United States	MidState Medical Center	Meriden	Connecticut
United States	Miami Cancer Institute, Baptist Health South Florida	Miami	Florida
United States	Pacific Cancer Care	Monterey	California
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Alvin J. Siteman Cancer Center Washington University	Saint Louis	Missouri
United States	UCLA Health	Santa Monica	California
United States	University of Washington/Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca

Countries where clinical trial is conducted

United States,  Belgium,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to 16 months (data cut-off)
Primary	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	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.	Up to 23 months (data cut-off)
Secondary	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	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.	Up to 16 months (data cut-off)
Secondary	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	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.	Up to 23 months (data cut-off)
Secondary	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	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.	Up to 16 months (data cut-off)
Secondary	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	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.	Up to 16 months (data cut-off)
Secondary	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	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.	Up to 23 months (data cut-off)
Secondary	Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	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.	Up to 16 months (data cut-off)
Secondary	Overall Survival (OS) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	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.	Up to 23 months (data cut-off)
Secondary	Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	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.	Up to 16 months (data cut-off)
Secondary	Duration of Response (DoR) Following Treatment With DS8201a in Participants With HER2-Positive Unresectable or Metastatic Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma	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.	Up to 23 months (data cut-off)