Clinical trial NCT05568095: A Clinical Trial of a New Combination Treatment, Domvanalimab and Zimberelimab, Plus Chemotherapy, for People With an Upper Gastrointestinal Tract Cancer That Cannot be Removed With Surgery That Has Spread to Other Parts of the Body
Official title: A Randomized, Open-Label, Multicenter Phase 3 Trial of Domvanalimab, Zimberelimab, and Chemotherapy Versus Nivolumab and Chemotherapy in Participants With Previously Untreated Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Advanced Upper Gastrointestinal Tract Adenocarcinoma
Keywords: Domvanalimab
Zimberelimab
Nivolumab
Advanced upper gastrointestinal tract adenocarcinoma
Gastroesophageal junction cancer
Esophageal adenocarcinoma
Gastric cancer
Gastric adenocarcinoma
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gilead Sciences
name: Taiho Pharmaceutical Co., Ltd.
First posted: 2022-10-05
Enrollment: 1040
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 randomized Phase 3 open-label study will compare the efficacy of the T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) monoclonal antibody domvanalimab, the anti programmed cell death protein 1 (PD-1) monoclonal antibody zimberelimab, and multiagent chemotherapy versus the anti PD-1 monoclonal antibody nivolumab and multiagent chemotherapy in the first-line treatment of participants with locally advanced unresectable or metastatic gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.


Eligibility criteria: Key Inclusion Criteria:

* Capable of giving signed informed consent which is in compliance with the requirements and restrictions listed in the informed consent form (ICF) and in protocol.
* Histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* At least one measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Key Exclusion Criteria:

* Underlying medical or psychiatric conditions that, in the investigator's or sponsor's opinion, will make the administration of study-specified therapy hazardous, including but not limited to:
* Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of randomization.
* Clinically significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease or cerebrovascular accident within 3 months prior to randomization, unstable angina, or new onset angina within 3 months prior to randomization, myocardial infarction within 6 months prior to randomization, or unstable arrhythmia within 3 months prior to randomization.
* History of prior solid-organ transplantation, including allogenic bone marrow transplantation.
* Dementia, psychiatric, or substance abuse disorders that would interfere with satisfying the requirements of the trial.
* Known human epidermal growth factor receptor 2 (HER-2) positive tumor.
* Known untreated, symptomatic, or actively progressing central nervous system (CNS) (brain) metastases. Participants with leptomeningeal metastases are excluded from enrollment.
* Received prior systemic treatment for locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma.
* Disease progression within 6 months of completion of neoadjuvant or adjuvant therapy.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Overall survival
timeFrame: From date of randomization until date of death from any cause (Approximately 15 months)]
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From date of randomization to date of the first documentation of disease progression or date of death from any cause, whichever comes first (Approximately 15 months)
measure: Objective response rate (ORR)
timeFrame: Proportion of randomized participants who achieved a confirmed best overall response of complete response (CR) or partial response (PR) (Approximately 15 months)
measure: Duration of response (DOR)
timeFrame: From the date of first confirmed response (CR or PR), until the date of first documented disease progression or date of death from any cause, whichever comes first (Approximately 15 months)
measure: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From on or after the date of first dose of any study treatment to the date of last study treatment specific safety follow-up or date of initiation of subsequent systemic anti-cancer therapy, whichever occurs first (Approximately 15 months)
measure: Time to first symptom deterioration in the FACT-Ga gastric cancer subscale.
timeFrame: From the date of randomization to change from baseline in subscale greater than or equal to the deterioration threshold, or death from any cause, whichever comes first (Approximately 15 months)
Other outcomes:
Locations:
city: Hot Springs
country: United States
facility: Genesis Cancer Center and Blood Institute - Hot Springs
state: Arkansas
city: Los Angeles
country: United States
facility: Kaiser Permanente - Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: University of California Irvine Health Chao Family Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Health - Santa Monica Cancer Care
state: California
city: Santa Monica
country: United States
facility: UCLA Ronald Reagan Med Ctr
state: California
city: New Haven
country: United States
facility: Smillow Cancer Hosp
state: Connecticut
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Fort Myers
country: United States
facility: SCRI - Florida Cancer Specialists - South Region Research Office
state: Florida
city: Saint Petersburg
country: United States
facility: SCRI - Florida Cancer Specialists - North Region Research Office
state: Florida
city: Tallahassee
country: United States
facility: SCRI - Florida Cancer Specialists - Panhandle Research Office
state: Florida
city: West Palm Beach
country: United States
facility: SCRI - Florida Cancer Specialists - East Region Research Office
state: Florida
city: Louisville
country: United States
facility: University of Louisville James Graham Brown Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute - Poplar Level Road
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Cancer Institute
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: Saint Louis Park
country: United States
facility: HealthPartners Cancer Center at Regions Hospital
state: Minnesota
city: Saint Louis Park
country: United States
facility: Regions Hospital
state: Minnesota
city: Mineola
country: United States
facility: Perlmutter Cancer Ctr NYU
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center - 38th Street
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - New York
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleavland Clin - Taussig Cancer Ctr
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clin - Fairview Hosp
state: Ohio
city: Columbus
country: United States
facility: Mark H. Zangmeister Cancer Center
state: Ohio
city: Mayfield Heights
country: United States
facility: Cleveland Clin-Hillcrest Hosp
state: Ohio
city: Portland
country: United States
facility: Prov Care Clinic - Westside
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center Oncology and Hematology Care Westside Portland
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris Road
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology - Chattanooga - Memorial Plaza
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville - Centennial
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: The Center for Cancer & Blood Disorders - Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Harris Health System
state: Texas
city: Fairfax
country: United States
facility: USOR - Virginia Cancer Specialists - Fairfax Office
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center - Seattle Cancer Care Alliance (SCCA) Location
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Clinical Cancer Center
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital Británico de Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar del Plata
city: Clayton
country: Australia
facility: Monash University
city: Gosford
country: Australia
facility: Gosford Hospital
city: Liverpool
country: Australia
facility: Liverpool Hospital
city: Murdoch
country: Australia
facility: Oncology West - Murdoch
city: Barretos
country: Brazil
facility: Fundação Pio XII - Hospital de Câncer de Barretos - Hospital de Amor
city: Ijuí
country: Brazil
facility: ONCOSITE - Centro de Pesquisa Clinica Em Oncologia Ltda.
city: Natal
country: Brazil
facility: Liga Contra o Câncer - Centro Avançado de Oncologia
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Câncer - Brazil
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre-Victoria General
city: Montreal
country: Canada
facility: CHUM
city: Montreal
country: Canada
facility: Hôpital Notre-Dame
city: Ottawa
country: Canada
facility: Ottawa Hospital - General Campus
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre - Bayview Campus
city: La Florida
country: Chile
facility: Icegclinic
city: Providencia
country: Chile
facility: Oncovida - Santiago
city: Puerto Montt
country: Chile
facility: Hospital Puerto Montt
city: Recoleta
country: Chile
facility: Bradford Hill Centro de Investigaciones Clinicas
city: Santiago
country: Chile
facility: Centro de Estudios Clínicos SAGA
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile - Escuela De Medicina - Clinica UC San Carlos de Apoq
city: Talca
country: Chile
facility: Clínica Universidad Católica del Maule - Talca
city: Bordeaux cedex
country: France
facility: Institut Bergonié
city: Brest
country: France
facility: Hôpital Morvan
city: Caen Cedex 5
country: France
facility: Centre de Lutte contre le Cancer - François Baclesse
city: Lille Cedex
country: France
facility: Hôpital Claude Huriez
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital de la Timone
city: Montpellier
country: France
facility: Institut Régional du Cancer de Montpellier
city: Plerin
country: France
facility: Centre Armoricain de Radiothérapie, d'Imagerie Médicale et d'Oncologie
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Kutaisi
country: Georgia
facility: Evex Hospitals - Kutaisi Referral Hospital
city: Tbilisi
country: Georgia
facility: LLC Todua Clinic
city: Tbilisi
country: Georgia
facility: Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
city: Tbilisi
country: Georgia
facility: New Vision University Hospital
city: Tbilisi
country: Georgia
facility: Multi-profile Clinic "New Hospitals"
city: Athens
country: Greece
facility: Evgenidion Clinic SA - Agia Trias
city: Nea Kifisia
country: Greece
facility: General Oncology Hospital of Kifisias "Agioi Anargyroi"
city: Neo Faliro
country: Greece
facility: Metropolitan Hospital
city: Thessaloniki
country: Greece
facility: BioClinic Thessaloniki
city: Guatemala city
country: Guatemala
facility: Medi-k Cayalá
city: Guatemala
country: Guatemala
facility: Clínica Privada Dr. Rixci Ramírez
city: Guatemala
country: Guatemala
facility: Grupo Medico Angeles
city: Guatemala
country: Guatemala
facility: INTEGRA Cancer Institute
city: Quetzaltenango
country: Guatemala
facility: Centro Regional de Sub Especialidades Médicas (CRESEM) SA
city: Happy Valley
country: Hong Kong
facility: Hong Kong Sanatorium and Hospital
city: Hong Kong
country: Hong Kong
facility: Humanity & Health Clinical Trial Centre
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital - Hong Kong
city: Tuen Mun
country: Hong Kong
facility: Tuen Mun Hospital
city: Budapest
country: Hungary
facility: Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet
city: Kecskemet
country: Hungary
facility: Bács-Kiskun Megyei Oktatókórház - Kecskemét
city: Pecs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petah Tikva
country: Israel
facility: Davidoff Cancer Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Firenze
country: Italy
facility: Azienda Ospedaliero - Universitaria Careggi
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milan
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
city: Rozzano
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale ? P.O. Santa Maria della Misericordia
city: Akashi City
country: Japan
facility: Hyogo Cancer Center
city: Bunkyo-ku
country: Japan
facility: University of Tokyo Hospital
city: Bunkyō-Ku
country: Japan
facility: Tokyo Metro Ctr
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Fukuoka-shi
country: Japan
facility: Kyushu Cancer Center
city: Ina
country: Japan
facility: Saitama Cancer Center
city: Kashiwa-shi
country: Japan
facility: Nat Cancer Ctr-Kashiwa Campus
city: Kawasaki
country: Japan
facility: St. Marianna Uni Hosp
city: Koto
country: Japan
facility: Cancer Inst Hosp of JFCR
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Matsuyama-Shi
country: Japan
facility: Shikoku Cancer Center
city: Matsuyama-Shi
country: Japan
facility: Shizuoka Cancer Center
city: Nagoya
country: Japan
facility: Aichi Cancer Center
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: Osaka Prefectural Hosp Org
city: Ota-shi
country: Japan
facility: Gunma Prefectural Cancer Ctr
city: Sapporo
country: Japan
facility: Teine Keijinkai Hospital
city: Tokyo
country: Japan
facility: National Cancer Ctr Hosp
city: Yokohama-Shi
country: Japan
facility: Kanagawa Cancer Center
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook Nat Uni Chilgok
city: Seongnam
country: Korea, Republic of
facility: Cha Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul Nat Uni Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Kaunas
country: Lithuania
facility: Kauno Klinikos
city: Klaipeda
country: Lithuania
facility: Klaipedos Universitetine Ligonine
city: Vilnius
country: Lithuania
facility: Nacionalinis Vėžio Institutas
city: Vilnius
country: Lithuania
facility: Vilniaus Universiteto Ligoninė Santariškių Klinikos
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: Pusat Perubatan Universiti Malaya
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: Colonia Centro
country: Mexico
facility: CLIMERS Clinical Medical Research
city: Merida
country: Mexico
facility: Centro de Atención e Investigación Clínica en Oncología
city: Mexico DF
country: Mexico
facility: Centro Especializado en Investigacion y Tratamiento Oncologicos SC
city: San Pedro Garza García
country: Mexico
facility: Hospital Zambrano Hellion TecSalud
city: Toluca de Lerdo
country: Mexico
facility: Centro Hemato - Oncológico Privado (CHOP)
city: Bellavista
country: Peru
facility: Hospital Nacional Daniel Alcides Carrión
city: San Isidro
country: Peru
facility: SANNA - Clínica El Golf
city: San Juan De Miraflores
country: Peru
facility: Hospital Maria Auxiliadora
city: Surquillo
country: Peru
facility: Instituto Nacional de Enfermedades Neoplásicas
city: Bacolod City
country: Philippines
facility: Dr Pablo O. Torre Memorial Hospital - Riverside Medical Center
city: Baguio
country: Philippines
facility: Baguio General Hospital and Medical Center
city: Cebu City
country: Philippines
facility: Cebu Doctors' University Hospital
city: Manila
country: Philippines
facility: Manila Doctors Hospital
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
city: Tychy
country: Poland
facility: Szpital Miejski w Tychach
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra
city: Lisboa
country: Portugal
facility: Fundação D. Anna de Sommer Champalimaud e Dr. Carlos Montez Champalimaud
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil
city: Baia Mare
country: Romania
facility: Spitalul Judetean de Urgenta
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic Prof. Dr. Ion Chiricuta
city: Cluj-Napoca
country: Romania
facility: Medisprof
city: Craiova
country: Romania
facility: Centrul De Oncologie Sf Nectarie
city: Florești
country: Romania
facility: Centrul de Radioterapie Amethyst Cluj
city: Iasi
country: Romania
facility: Centrul de Oncologie Euroclinic
city: Suceava
country: Romania
facility: Clinica SIGMedical
city: Belgrade
country: Serbia
facility: Institute of Oncology and Radiology of Serbia (Institut za onkologiju i radiologiju Srbije)
city: Belgrade
country: Serbia
facility: University Hospital Medical Center (KBC) Bezanijska Kosa
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Bang Phlat
country: Thailand
facility: Faculty of Medicine Siriraj Hospital
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital
city: Ubon Ratchathani
country: Thailand
facility: Sunpasitthiprasong Hospital
city: Adana
country: Turkey
facility: T.C. Saglik Bakanligi Adana Sehir Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: T.C. Saglik Bakanligi - Istanbul Il Saglik Mudurlugu - Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
city: Izmit
country: Turkey
facility: Kocaeli Üniversitesi Araştırma ve Uygulama Hastanesi
city: Malatya
country: Turkey
facility: Inönü Üniversitesi Turgut Özal Tıp Merkezi
city: Mamak
country: Turkey
facility: Ankara Üniversitesi Tıp Fakültesi - Cebeci Araştırma ve Uygulama Hastanesi
city: Van
country: Turkey
facility: Van Yüzüncü Yıl Üniversitesi Dursun Odabaş Tıp Merkezi
city: Yakutiye
country: Turkey
facility: Ataturk Universitesi Arastirma Hastanesi
city: Yüreğir
country: Turkey
facility: Başkent Üniversitesi Adana Dr Turgut Noyan Uygulama ve Araştirma Merkezi
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute London
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Arcus Biosciences
name: Medical Director
role: STUDY_DIRECTOR
References: