Study Stopped
Based on a review of data conducted by the Independent Data Monitoring Committee (IDMC), Sponsor decided to discontinue this study as the study was unlikely to achieve the primary objective of overall survival.
Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC
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
2 other identifiers
interventional
309
15 countries
99
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2019
Typical duration for phase_2
99 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 22, 2019
CompletedFirst Posted
Study publicly available on registry
August 26, 2019
CompletedStudy Start
First participant enrolled
September 20, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 20, 2021
CompletedResults Posted
Study results publicly available
June 13, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
November 10, 2022
CompletedNovember 14, 2023
October 1, 2023
1.7 years
August 22, 2019
May 16, 2022
October 26, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Safety Run-in Part: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
A DLT is a toxicity related to the study intervention that meets the following criteria as evaluated in the open-label, safety run-in: Grade 3 or 4 Immune-related adverse event (irAE) that needs permanent discontinuation of M7824 treatment; a malignant skin lesion induced by M7824 that is local and can be resected with a negative resection margin is not a DLT; Grade 3 or 4 nonhematologic toxicity other than irAE, A life threatening hematological toxicity (unless clearly attributable to chemotherapy alone), which is hardly medically manageable, including a bleeding event resulting in urgent intervention and admission to an intensive care unit and Grade 5 toxicity.
Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days)
Double-blind Part: Overall Survival
Overall Survival was defined as the time from study day 1 to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method.
Time from study day 1 up to data cutoff (assessed up to 609 days)
Secondary Outcomes (7)
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
Time from first treatment up to data cutoff (assessed up to 609 days)
Safety Run-in Part: Number of Participants With Grade Greater Than or Equal (>=) 3 Laboratory Abnormalities
Time from first treatment up to data cutoff (assessed up to 609 days)
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)
Time from randomization of study drug until the first documentation of PD or death, assessed up to 609 days
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)
Time from randomization of study drug up to data cut off (assessed up to 609 days)
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)
From first documented objective response to PD or death due to any cause, assessed up to 609 days
- +2 more secondary outcomes
Study Arms (3)
Safety Run-In Part: M7824 + Gemcitabine + Cisplatin
EXPERIMENTALDouble-blinded Part: M7824 + Gemcitabine + Cisplatin
EXPERIMENTALDouble-blinded Part: Placebo + Gemcitabine + Cisplatin
PLACEBO COMPARATORInterventions
Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of Complete Response), otherwise until criterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 milligram per meter square (mg/m\^2) and 25 mg/m\^2 respectively on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks.
Participants received intravenous infusion of M7824 matched placebo, once every 3 weeks (Q3W) until 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met.
Gemcitabine was received intravenously at a dose of 1000 milligram per meter square (mg/m\^2) on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks (Q3W).
Cisplatin was received intravenously at a dose of 25 mg/m\^2 on Day 1 and Day 8 of 21-day cycle, for 8 cycles every 3 weeks (Q3W).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (99)
Ironwood Cancer & Research Centers - Chandler II
Chandler, Arizona, 85224, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
Mayo Clinic Arizona
Phoenix, Arizona, 85054, United States
Beverly Hills Cancer Center
Beverly Hills, California, 90211, United States
Mayo Clinic in Florida - Department of Neurology
Jacksonville, Florida, 32224, United States
Mount Sinai Medical Center
Miami Beach, Florida, 33140, United States
University of Kansas Medical Center Research Institute, Inc. - University of Kansas Cancer Center/Bloch Pavilion
Westwood, Kansas, 66216, United States
Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, 21287, United States
Mayo Clinic - Rochester
Rochester, Minnesota, 55905, United States
Methodist Transplant Physicians
Dallas, Texas, 75203, United States
MD Anderson Cancer Center - Unit 429
Houston, Texas, 77030, United States
Renovatio Clinical - CENTRAL SITE
The Woodlands, Texas, 77380, United States
Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo
Ciudad Autonoma Buenos Aires, Argentina
Instituto de Investigaciones Metabolicas (IDIM)
Ciudad Autonoma Buenos Aires, Argentina
Instituto Medico Especializado Alexander Fleming
Ciudad Autonoma Buenos Aires, Argentina
Centro Oncologico Riojano Integral (CORI)
La Rioja, Argentina
CEDIT
Salta, Argentina
Centro Medico San Roque S.R.L.
San Miguel de Tucumán, Argentina
Fundacion ARS Medica
San Salvador de Jujuy, Argentina
Blacktown Hospital - PARENT
Blacktown, Australia
Monash Health
Clayton, Australia
Epworth Freemasons
Melbourne, Australia
Icon Cancer Care South Brisbane
South Brisbane, Australia
Hospital de Câncer de Barretos - Fundação Pio XII
Barretos, Brazil
INCA - Instituto Nacional de Câncer
Rio de Janeiro, Brazil
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
Sao Jose Rio Preto, Brazil
A. C. Camargo Cancer Center
São Paulo, Brazil
ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira
São Paulo, Brazil
IC la serena Research
La Serena, Chile
Centro de Investigación Clínica Bradford Hill
Santiago, Chile
Hospital Clínico Universidad de Chile
Santiago, Chile
Prosalud
Santiago, Chile
Instituto Clinico Oncologico del Sur (ICOS)
Temuco, Chile
Beijing Cancer Hospital
Beijing, China
Beijing Chao Yang Hospital
Beijing, China
Beijing Friendship Hospital, Capital Medical University
Beijing, China
West China Hospital, Sichuan University
Chengdu, China
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
Hangzhou, China
The Affiliated Hospital of Qingdao University
Qingdao, China
Fudan University Shanghai Cancer Hospital
Shanghai, China
The Second Affiliated Hospital of Soochow University
Suzhou, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, China
ICO - Site Paul Papin - service d'oncologie medicale
Angers, France
Centre Georges François Leclerc - Oncologie Médicale
Dijon, France
CHU Lille - Hôpital Claude Huriez
Lille, France
ICO - Site René Gauducheau
Saint-Herblain, France
CHU de Toulouse - Hôpital Ranguei
Toulouse, France
Vivantes Klinikum Neukoelln - Haematologie und Onkologie
Berlin, Germany
Universitaetsklinikum Bonn AoeR - Medizinische Klinik I Gastroenterologie
Bonn, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden - Medizinische Klinik I
Dresden, Germany
Klinikum der Johann Wolfgang Goethe-Universitaet
Frankfurt, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - Medizinische Klinik I - HCC Ambulanz
Mainz, Germany
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
Milan, Italy
IOV - Istituto Oncologico Veneto IRCCS - S.Semplice Dip.Oncologia dei Melanomi
Padua, Italy
Università Campus Bio-Medico di Roma
Roma, Italy
Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) - UOC Oncologia
Verona, Italy
Chiba Cancer Center
Chiba, Japan
National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology
Chūōku, Japan
NHO Kyushu Cancer Center - Dept of Gastroenterology/Hepatology/Pancreatology
Fukuoka, Japan
National Cancer Center Hospital East
Kashiwa-shi, Japan
Cancer Institute Hospital of JFCR - Dept of Hepato,Biliary and Pancreatic Medicine
Kōtoku, Japan
Kyorin University Hospital
Mitaka-shi, Japan
Aichi Cancer Center Hospital
Nagoya, Japan
Osaka City University Hospital
Osaka, Japan
Kindai University Hospital
Osakasayama-shi, Japan
Kanagawa Cancer Center
Yokohama, Japan
Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
Gliwice, Poland
Pratia
Krakow, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, Poland
ETG Zamosc
Zamość, Poland
Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
Daejeon, South Korea
Seoul National University Bundang Hospital
Seongnam-si, South Korea
Asan Medical Center
Seoul, South Korea
Korea University Anam Hospital
Seoul, South Korea
Korea University Guro Hospital
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
Severance Hospital, Yonsei University Health System
Seoul, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, South Korea
Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia
Barcelona, Spain
Hospital Universitari Vall d'Hebron - Dept of Oncology
Barcelona, Spain
Hospital San Pedro de Alcantara - Servicio de Oncologia
Cáceres, Spain
Hospital Universitario Reina Sofia - Dept of Oncology
Córdoba, Spain
ICO l´Hospitalet - Hospital Duran i Reynals
L'Hospitalet de Llobregat, Spain
Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
Madrid, Spain
Hospital Universitario Clinico San Carlos - Servicio de Oncologia
Madrid, Spain
Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
Madrid, Spain
Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
Valencia, Spain
Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
Valencia, Spain
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, Taiwan
China Medical University Hospital
Taichung, Taiwan
Taichung Veterans General Hospital
Taichung, Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Chang Gung Memorial Hospital, Linkou
Taoyuan District, Taiwan
The Christie - Dept of Oncology
Manchester, United Kingdom
Related Publications (1)
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.
PMID: 32461347RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Data collection and analysis of Pharmacokinetics and Immunogenicity were omitted and not conducted due to business reason.
Results Point of Contact
- Title
- Communication Center
- Organization
- Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study Officials
- STUDY DIRECTOR
Medical Responsible
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 22, 2019
First Posted
August 26, 2019
Study Start
September 20, 2019
Primary Completion
May 20, 2021
Study Completion
November 10, 2022
Last Updated
November 14, 2023
Results First Posted
June 13, 2022
Record last verified: 2023-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union.
- Access Criteria
- Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21