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

Phase 2

Completed

• Conditions: Adenocarcinoma Gastric Stage IV With Metastases; Adenocarcinoma - GEJ
• Interventions: Drug: Trastuzumab deruxtecan

• Registration Number: NCT04014075
• Lead Sponsor: Daiichi Sankyo

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 available

Study Timeline

• Study First Submitted: 2019-07-08
• Study First Submitted QC: 2019-07-08
• Study First Posted: 2019-07-10
• Study Start: 2019-11-26
• Primary Completion: 2021-11-08
• Results First Submitted: 2021-12-14
• Results First Submitted QC: 2021-12-14
• Results First Posted: 2022-01-12
• Study Completion: 2024-02-13
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-05
• Last Update Posted: 2024-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All participants	Trastuzumab deruxtecan	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.

Primary Outcome Measures

Name	Time	Method
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	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.

Secondary Outcome Measures

Name	Time	Method
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	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	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	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	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	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.

Trial Locations

Locations (36)

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

USC Norris Comprehensive Cancer Center Hospital; 🇺🇸 Los Angeles, California, United States

UCLA Health; 🇺🇸 Santa Monica, California, United States

Alvin J. Siteman Cancer Center Washington University; 🇺🇸 Saint Louis, Missouri, United States

Northwell Health Cancer Institute; 🇺🇸 Lake Success, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Lehigh Valley Health Network; 🇺🇸 Allentown, Pennsylvania, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Hospital la Paz; 🇪🇸 Madrid, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Biomedical Research Institute Hospital de Valencia; 🇪🇸 Valencia, Spain

MidState Medical Center; 🇺🇸 Meriden, Connecticut, United States

UZ Leuven; 🇧🇪 Leuven, Belgium

The Hospital of Central Connecticut; 🇺🇸 New Britain, Connecticut, United States

Hopital de Jolimont; 🇧🇪 Haine-Saint-Paul, Belgium

Massachusetts General Hospital (MGH); 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center (BIDMC); 🇺🇸 Boston, Massachusetts, United States

Smilow Cancer Hospital at Yale-New Haven; 🇺🇸 New Haven, Connecticut, United States

UCL St-Luc; 🇧🇪 Brussels, Belgium

Pacific Cancer Care; 🇺🇸 Monterey, California, United States

City of Hope Medical Center; 🇺🇸 Duarte, California, United States

Kansas University Cancer Center; 🇺🇸 Kansas City, Kansas, United States

University of Chicago Medical Center UCMC Duchossois Center for Advanced Medicine DCAM; 🇺🇸 Chicago, Illinois, United States

Miami Cancer Institute, Baptist Health South Florida; 🇺🇸 Miami, Florida, United States

University of Washington/Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Azienda Ospedaliero Universitaria di Modena Policlinico; 🇮🇹 Modena, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

Asst Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Italy

Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO); 🇪🇸 Barcelona, Spain

The Royal Marsden Hospital; 🇬🇧 Sutton, United Kingdom

Institut Catalan de Oncologia Hospital Duran i Reynals; 🇪🇸 Barcelona, Spain

Cambridge University Hospitals NHS Foundation Trust; 🇬🇧 Cambridge, United Kingdom

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

Oncology Institute Veneto IOVIRCCS; 🇮🇹 Padua, Italy

Christie Hospital; 🇬🇧 Manchester, United Kingdom

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States