Clinical trial NCT04066491: Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC
Official title: A Phase II/III, Multicenter, Randomized, Placebo-controlled Study of Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) as First-line Treatment of Biliary Tract Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Biliary Tract Cancer
Cholangiocarcinoma
Gallbladder Cancer
Keywords: Metastatic Biliary Tract Cancer
Cholangiocarcinoma
Gallbladder Cancer
Ampullary cancer
M7824
Bintrafusp alfa
Transforming growth factor-beta
Programmed death-ligand 1
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2019-08-26
Enrollment: 309
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: Study consisted of an open-label, safety run-in part and a randomized, double-blind, placebo-controlled Phase 2/3 part. In the Phase 2/3 part, the study was evaluated whether bintrafusp alfa in combination with the current standard of care (SoC) (gemcitabine plus cisplatin) improves overall survival (OS) in chemotherapy and immunotherapy-naïve participants with locally advanced or metastatic Biliary Tract Cancer (BTC) compared to placebo, gemcitabine and cisplatin.


Eligibility criteria: Inclusion Criteria:

* Are participants with histologically or cytologically confirmed locally advanced or metastatic BTC
* Participants must have available tumor tissue (primary or metastatic) (archival or fresh biopsies) before the first administration of study treatment
* At least 1 measurable lesion according to RECIST 1.1
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study entry and at Week 1, Day 1 prior to dosing
* Life expectancy of \>= 12 weeks, as judged by the Investigator
* Adequate hematological function, hepatic function, renal function, coagulation function as defined in the protocol
* Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Previous and/or intercurrent cancers
* Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression
* Participants with symptomatic central nervous system (CNS) metastases
* Significant acute or chronic infection including known history of positive test for human immunodeficiency virus (HIV), active tuberculosis, uncontrolled biliary infection and active bacterial or fungal infection requiring systemic therapy (with the exception of hepatitis B and hepatitis C) requiring systemic therapy at study entry and at Week 1 Day 1 prior to dosing.
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* History of or concurrent interstitial lung disease
* History of hypersensitivity reactions to bintrafusp alfa, anaphylaxis, or recent (within 5 months) uncontrolled asthma, cardiovascular/cerebrovascular disease
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before randomization
* Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints)
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Safety Run-in Part: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days)
measure: Double-blind Part: Overall Survival
timeFrame: Time from study day 1 up to data cutoff (assessed up to 609 days)
Secondary outcomes:
measure: Safety Run-in Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs) and Treatment Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
timeFrame: Time from first treatment up to data cutoff (assessed up to 609 days)
measure: Safety Run-in Part: Number of Participants With Grade Greater Than or Equal (>=) 3 Laboratory Abnormalities
timeFrame: Time from first treatment up to data cutoff (assessed up to 609 days)
measure: Double-blind Part: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
timeFrame: Time from randomization of study drug until the first documentation of PD or death, assessed up to 609 days
measure: Double-blind Part: Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
timeFrame: Time from randomization of study drug up to data cut off (assessed up to 609 days)
measure: Double-blind Part: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
timeFrame: From first documented objective response to PD or death due to any cause, assessed up to 609 days
measure: Double-blind Part: Durable Response of at Least 6 Months According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
timeFrame: Time from first treatment assessed up to 1148 days
measure: Double-blind Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs), Treatment Related TEAEs and Adverse Events of Special Interest (AESIs) According to NCI-CTCAE Version 5.0
timeFrame: Time from first treatment up to data cutoff (assessed up to 609 days)
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer &amp; Research Centers - Chandler II
state: Arizona
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida - Department of Neurology
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Westwood
country: United States
facility: University of Kansas Medical Center Research Institute, Inc. - University of Kansas Cancer Center/Bloch Pavilion
state: Kansas
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at John Hopkins
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Dallas
country: United States
facility: Methodist Transplant Physicians
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center - Unit 429
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical - CENTRAL SITE
state: Texas
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Metabolicas (IDIM)
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (CORI)
city: Salta
country: Argentina
facility: CEDIT
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico San Roque S.R.L.
city: San Salvador de Jujuy
country: Argentina
facility: Fundacion ARS Medica
city: Blacktown
country: Australia
facility: Blacktown Hospital - PARENT
city: Clayton
country: Australia
facility: Monash Health
city: Melbourne
country: Australia
facility: Epworth Freemasons
city: South Brisbane
country: Australia
facility: Icon Cancer Care South Brisbane
city: Barretos
country: Brazil
facility: Hospital de Câncer de Barretos - Fundação Pio XII
city: Rio de Janeiro
country: Brazil
facility: INCA - Instituto Nacional de Câncer
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
city: Sao Jose Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
city: São Paulo
country: Brazil
facility: A. C. Camargo Cancer Center
city: São Paulo
country: Brazil
facility: ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira
city: La Serena
country: Chile
facility: IC la serena Research
city: Santiago
country: Chile
facility: Centro de Investigación Clínica Bradford Hill
city: Santiago
country: Chile
facility: Hospital Clínico Universidad de Chile
city: Santiago
country: Chile
facility: Prosalud
city: Temuco
country: Chile
facility: Instituto Clinico Oncologico del Sur (ICOS)
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Chao Yang Hospital
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Hospital
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Angers Cedex 2
country: France
facility: ICO - Site Paul Papin - service d'oncologie medicale
city: Dijon cedex
country: France
facility: Centre Georges François Leclerc - Oncologie Médicale
city: Lille cedex
country: France
facility: CHU Lille - Hôpital Claude Huriez
city: Saint Herblain
country: France
facility: ICO - Site René Gauducheau
city: Toulouse Cedex 9
country: France
facility: CHU de Toulouse - Hôpital Ranguei
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukoelln - Haematologie und Onkologie
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn AoeR - Medizinische Klinik I Gastroenterologie
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden - Medizinische Klinik I
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - Medizinische Klinik I - HCC Ambulanz
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori Milano
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS - S.Semplice Dip.Oncologia dei Melanomi
city: Roma
country: Italy
facility: Università Campus Bio-Medico di Roma
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) - UOC Oncologia
city: Chiba-shi
country: Japan
facility: Chiba Cancer Center
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology
city: Fukuoka-shi
country: Japan
facility: NHO Kyushu Cancer Center - Dept of Gastroenterology/Hepatology/Pancreatology
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR - Dept of Hepato,Biliary and Pancreatic Medicine
city: Mitaka-shi
country: Japan
facility: Kyorin University Hospital
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital
city: Osaka-shi
country: Japan
facility: Osaka City University Hospital
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
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 National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Gliwice
country: Poland
facility: Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
city: Krakow
country: Poland
facility: Pratia
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
city: Zamosc
country: Poland
facility: ETG Zamosc
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Dept of Oncology
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara - Servicio de Oncologia
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia - Dept of Oncology
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO l´Hospitalet - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos - Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Manchester
country: United Kingdom
facility: The Christie - Dept of Oncology
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Yoo C, Oh DY, Choi HJ, Kudo M, Ueno M, Kondo S, Chen LT, Osada M, Helwig C, Dussault I, Ikeda M. Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with pretreated biliary tract cancer. J Immunother Cancer. 2020 May;8(1):e000564. doi: 10.1136/jitc-2020-000564.