Clinical trial NCT04704934: Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma After Progression on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)
Official title: A Phase 3, Multicenter, 2-Arm Randomized, Open-Label Study of Trastuzumab Deruxtecan in Subjects With HER2-Positive Metastatic and/or Unresectable Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma Subjects Who Have Progressed on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Gastric Cancer, Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Keywords: Gastric Cancer, Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Trastuzumab deruxtecan
T-DXd
DS-8201a
Ramucirumab
Paclitaxel
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2021-01-12
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with ramucirumab and paclitaxel (Ram + PTX) in participants with HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma who have progressed on or after a trastuzumab-containing regimen and have not received any additional systemic therapy.

Detailed description: This study will assess the efficacy and safety of T-DXd compared with Ram + PTX in participants with HER2-positive (defined as immunohistochemistry \[IHC\] 3+ or IHC 2+/in situ hybridization \[ISH\]+) gastric or GEJ adenocarcinoma (based on \[American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines who have progressed on or after a trastuzumab-containing regimen and have not received any additional systemic therapy. Participants will be randomized 1:1 to either T-DXd or Ram + PTX treatment. The primary objective will assess overall survival. Secondary objectives will further assess progression-free survival, objective response rate, duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity of T-DXd.

Eligibility criteria: Inclusion Criteria:

* Adults (according to local regulation) and able to provide informed consent for study participation.
* Pathologically documented gastric and GEJ adenocarcinoma that has been previously treated in the metastatic setting (unresectable, locally advanced, or metastatic disease).
* Progression on or after first-line therapy with a trastuzumab or approved trastuzumab biosimilar-containing regimen. Note: Prior neoadjuvant or adjuvant therapy with a trastuzumab-containing regimen can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy. Prior neoadjuvant or adjuvant therapy that does not include trastuzumab will not be counted as a line of therapy regardless of the progression status of the subject.
* Locally or centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH) as classified by ASCO-CAP on a tumor biopsy obtained after progression on or after a first-line trastuzumab or approved trastuzumab biosimilar-containing regimen.
* Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening.
* Adequate bone marrow, renal, hepatic function, and blood clotting function within 14 days of randomization.

Exclusion Criteria:

* Use of anticancer therapy after trastuzumab-containing treatment
* Medical history of myocardial infarction (MI) within 6 months before randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV).
* Has a QT interval corrected by Fridericia's formula (QTcF) prolongation to \>470 msec (female subjects) or \>450 msec (male subjects) based on average of the Screening triplicate12-lead ECG.
* Has a history of (non-infectious) interstitial lung disease (ILD/pneumonitis) that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
* Any autoimmune, connective tissue or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented (or a suspicion of) pulmonary involvement at the time of Screening.
* Prior complete pneumonectomy.
* 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.
* Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated.
* History of severe hypersensitivity reactions to either the T-DXd or inactive ingredients in T-DXd.
* History of severe hypersensitivity reactions to other monoclonal antibodies, including ramucirumab or to any of its excipients.
* Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy.
* Current uncontrolled infection requiring antibiotics, antivirals, or antifungals or an unexplained fever \>38.0°C during Screening visits or on the first scheduled day of dosing (at the discretion of the Investigator, participants with tumor fever may be enrolled), which in the Investigator's opinion might compromise the participant's participation in the study or affect the study outcome
* Clinically significant gastrointestinal disorder (eg, including hepatic disorders, bleeding, inflammation, occlusion, ileus, diarrhea Grade \>1, jaundice, intestinal paralysis, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction) in the opinion of Investigator
* Has history of receiving live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention

Primary outcomes:
measure: Overall Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
timeFrame: Time from date of randomization until death (due to any cause), up to approximately 36 months
Secondary outcomes:
measure: Progression-free Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
timeFrame: Time from date of randomization until first objective radiographic disease progression or death (due to any cause) whichever occurs first, up to approximately 36 months
measure: Objective Response Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
timeFrame: From start of treatment to date of documented disease progression, up to approximately 36 months
measure: Duration of Response in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
timeFrame: Time from initial response (CR or PR) to date of documented disease progression or death (due to any cause) whichever occurs first, up to approximately 36 months
measure: Disease Control Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel
timeFrame: From start of treatment to date of documented disease progression, up to approximately 36 months
measure: Incidence of Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI), and Physical Examination Findings
timeFrame: From time subjects signs informed consent form up to 40 days after last study dose
measure: Serum Concentrations for Trastuzumab Deruxtecan, total anti-HER2 antibody, and Active Metabolite MAAA-1181a
timeFrame: Cycles 1-4 and subsequent cycles on Day 1 pre- and post-infusion (each cycle is 28 days)
measure: Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
timeFrame: Cycles 1, 2, and 4 on Day 1 pre-infusion, then every 4 cycles on Day 1 pre-infusion, 40 day follow up until death, withdrawal of consent, or lost to follow up whichever occurs first (each cycle is 28 days)
measure: Percentage of Participants Who Have Treatment-emergent ADAs
timeFrame: Cycles 1, 2, and 4 on Day 1 pre-infusion, then every 4 cycles on Day 1 pre-infusion, 40 day follow up until death, withdrawal of consent, or lost to follow up whichever occurs first (each cycle is 28 days)
Other outcomes:
Locations:
city: Colegiales
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming
state: Caba
city: Nueva Cordoba
country: Argentina
facility: IONC Instituto Oncologico de Cordoba - Fundacion Richardet Longo
state: Cordoba
city: San Miguel De Tucumán
country: Argentina
facility: Exelsus
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Fundacion Cenit
city: Brussels
country: Belgium
facility: UCL St. Luc
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Haine-Saint-Paul
country: Belgium
facility: Pôle Hospitalier Jolimont
city: Leuven
country: Belgium
facility: UZ Leuven
city: Belo Horizonte
country: Brazil
facility: PERSONAL - Oncologia de Precisao e Personalizada
city: Brasilia
country: Brazil
facility: Hospital Sirio Libanes
city: Ijui
country: Brazil
facility: ONCOSITE - Centro de Pesquisa Clinica em Oncologia LTDA
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
city: Temuco
country: Chile
facility: SIM Centro de Investigacion Clinica
state: Cautin
city: Santiago
country: Chile
facility: Fundacion Arturo Lopez Perez
state: Region Metropolitana
city: Santiago
country: Chile
facility: Clinica San Carlos de Apoquindo
state: Region Metropolitana
city: Heifi
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Fuzhou
country: China
facility: Fujian Medical University - Fujian Provincial Cancer Hospital
state: Fuijan
city: Xiamen
country: China
facility: Xiamen University - The First Affiliated Hospital
state: Fujian
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: 1Affiliated H of Sun Yat Sen U
state: Guangdong
city: Shijiazhuang
country: China
facility: Hebei Medical Univ 4th Hosp
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changshan
country: China
facility: Zhongnan univ Xiangya hosp
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hosp
state: Jiangsu
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Shenyang
country: China
facility: 1st Hosp of China Medical Univ
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital & Institute
state: Shandong
city: Shanghai
country: China
facility: Zhongshan Hosp Fudan Univ
state: Shanghai
city: Shanghai
country: China
facility: Shanghai First People's Hosp
state: Shanghai
city: Urumqi
country: China
facility: Xinjiang Medical University - Cancer Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: Zhejiang Medical University - Zhejiang Cancer Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Peking Univ 3rd Hosp
city: Changchun
country: China
facility: The 1st Hospital of Jilin Univ
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
city: Linyi
country: China
facility: Linyi Cancer Hospital
city: Nanchang
country: China
facility: 1 Affiliated H of Nanchang U
city: Shanghai
country: China
facility: Fudan University - Shanghai Cancer Center
city: Besancon
country: France
facility: CHU Besançon
city: Brest
country: France
facility: CHRU
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon Cedex 08
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Hopital de la Timone
city: Montpellier
country: France
facility: Institut de Recherche en Cancerologie de Montpellier IRCM
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: L Institut Mutualiste Montsouris
city: Paris
country: France
facility: Hopital Europeen G. Pompidou
city: Saint-Priest-en-Jarez
country: France
facility: Pharmacie ICLN
city: Villejuif
country: France
facility: Gustave Roussy, étage -1.
city: Berlin
country: Germany
facility: Charité-Unimedizin Berlin
city: Dresden Sachsen
country: Germany
facility: Uniklinikum Carl-Gustav-Carus
city: Essen
country: Germany
facility: Evang. Klin. Essen-Mitte gGmbH
city: Frankfurt Am Main Hessen
country: Germany
facility: Ins. für klinische onk. Forschung
city: Hamburg
country: Germany
facility: Häm-Onk. Praxis Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Tumorzentrum Altona
city: Kln Nordrhein-westfalen
country: Germany
facility: Uni zu Koln-Unikl. Koln
city: Leipzig
country: Germany
facility: Universitares Krebszentrum
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: The Chinese University of Hong Kong (CUHK) - Prince of Wales Hospital (PWH) - Vascular and Interventional Radiology Foundation (VIRF) Clinical Science Centre
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszs. K
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai
city: Szekszard
country: Hungary
facility: Tolna M. Balassa Janos Korhaz
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Tallaght University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Be'er-Sheva Southern
country: Israel
facility: Soroka Univ Medical CTR
city: Petach Tikva
country: Israel
facility: Davidoff Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Barone
country: Italy
facility: AOU Pisana
city: Candiolo
country: Italy
facility: IRCC-FPO Candiolo
city: Catanzaro
country: Italy
facility: AOU Mater Domini
city: Milano
country: Italy
facility: San Raffaele Hospital
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia S.r.L Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini
city: Milan
country: Italy
facility: Ospedale Niguarda
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena
city: Napoli
country: Italy
facility: Aou Vanvitelli
city: Padua
country: Italy
facility: Istituto Oncologico Veneto
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichia
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
city: Chuo Ku
country: Japan
facility: Osaka International Cancer Institute
city: Gifu
country: Japan
facility: Gifu University Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
city: Kochi
country: Japan
facility: Kochi Health Sciences Center
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Suita
country: Japan
facility: Osaka University Hospital
city: Ōsaka-sayama
country: Japan
facility: Kindai University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook Nat Uni Chilgok Hos
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul Nati Univ Bundang Hosp
city: Seoul
country: Korea, Republic of
facility: Korea Univ Anam Hosp
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St. Marys Hospital
city: Seoul
country: Korea, Republic of
facility: Chonbuk National University Hospital - Jeonbuk Regional Cancer Center
city: Warszawa
country: Poland
facility: Sklodowska-Curie Inst Oncology
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im.Mikulicza-Radeckiego
city: Creixomil E Mariz
country: Portugal
facility: Hospital Sra da Oliveira
city: Porto
country: Portugal
facility: Instituto Portugues De Oncologia Do Porto Francisco Gentil, E.P.E.
city: Vila Real
country: Portugal
facility: C Hosp Tras Montes Alto Douro
city: Baia Mare
country: Romania
facility: S.C. Oncopremium-Team SRL
city: Bucharest
country: Romania
facility: Institutul Oncologic Prof. Dr. Alexandru Trestiorean Bucuresti IOB
city: Cluj-Napoca
country: Romania
facility: S.C. Medisprof SRL
city: Craiova
country: Romania
facility: Centrul de Oncologie Sf. Nectarie
city: Chelyabinsk
country: Russian Federation
facility: SBIH Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine
city: Saint-Petersburg
country: Russian Federation
facility: City Clinical Oncology Dispensary
city: St.Petersburg
country: Russian Federation
facility: Private Medical Institution "Euromedservice"
city: Ufa
country: Russian Federation
facility: Republican Clinical Oncology Dispensary
city: Singapore
country: Singapore
facility: National Univ Cancer Inst SGP
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Madrid
country: Spain
facility: H. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp Univ Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Pamplona
country: Spain
facility: Hospital de Navarra
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
city: Valencia
country: Spain
facility: H. Clinico U. de Valencia
city: Kaohsiung
country: Taiwan
facility: KMUH
city: Kaohsiung
country: Taiwan
facility: CGMF-Kaohsiung Branch
city: Taichung
country: Taiwan
facility: China Medical Univ Hosp
city: Tainan
country: Taiwan
facility: National Cheng Kung Univ Hosp
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital NTUH
city: Taipei
country: Taiwan
facility: MacKay Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hosp
city: Taoyuan
country: Taiwan
facility: CGMF-Linkou Branch
city: Adana
country: Turkey
facility: SBU Adana Sehir Hastanesi
city: Edirne
country: Turkey
facility: Trakya Universitesi Balkan
city: Istanbul
country: Turkey
facility: Suleyman Yalcin Seh. Hast.
city: Malatya
country: Turkey
facility: Inonu Uni. Turgut Ozal Tip
city: Kyiv
country: Ukraine
facility: National Cancer Institute
city: Kyiv
country: Ukraine
facility: MedicalCenter ASKLEPION LLC
city: Zaporizhzhia
country: Ukraine
facility: LLC "Oncolife"
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham UHB NHS Foundation Trust - Queen Elizabeth Hospital Birmingham QEHB
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: Velindre NHS Trust - Velindre Cancer Centre VCC
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: UCLH Trust
city: London
country: United Kingdom
facility: Royal Marsden NHS
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Oxford
country: United Kingdom
facility: University of Oxford, The Churchill Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Sutton
city: West Yorkshire
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: