Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC

NCT ID: NCT04066491

Last Updated: 2023-11-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

309 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-20

Study Completion Date

2022-11-10

Brief Summary

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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.

Detailed Description

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Conditions

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Biliary Tract Cancer Cholangiocarcinoma Gallbladder Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Safety Run-In Part: M7824 + Gemcitabine + Cisplatin

Group Type EXPERIMENTAL

M7824

Intervention Type DRUG

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.

Gemcitabine

Intervention Type DRUG

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

Intervention Type DRUG

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).

Double-blinded Part: M7824 + Gemcitabine + Cisplatin

Group Type EXPERIMENTAL

M7824

Intervention Type DRUG

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.

Gemcitabine

Intervention Type DRUG

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

Intervention Type DRUG

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).

Double-blinded Part: Placebo + Gemcitabine + Cisplatin

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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).

Interventions

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M7824

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Gemcitabine

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).

Intervention Type DRUG

Cisplatin

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).

Intervention Type DRUG

Eligibility Criteria

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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

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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

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Ironwood Cancer & Research Centers - Chandler II

Chandler, Arizona, United States

Site Status

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status

Beverly Hills Cancer Center

Beverly Hills, California, United States

Site Status

Mayo Clinic in Florida - Department of Neurology

Jacksonville, Florida, United States

Site Status

Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

University of Kansas Medical Center Research Institute, Inc. - University of Kansas Cancer Center/Bloch Pavilion

Westwood, Kansas, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at John Hopkins

Baltimore, Maryland, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Methodist Transplant Physicians

Dallas, Texas, United States

Site Status

MD Anderson Cancer Center - Unit 429

Houston, Texas, United States

Site Status

Renovatio Clinical - CENTRAL SITE

The Woodlands, Texas, United States

Site Status

Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo

Ciudad Autonoma Buenos Aires, , Argentina

Site Status

Instituto de Investigaciones Metabolicas (IDIM)

Ciudad Autonoma Buenos Aires, , Argentina

Site Status

Instituto Medico Especializado Alexander Fleming

Ciudad Autonoma Buenos Aires, , Argentina

Site Status

Centro Oncologico Riojano Integral (CORI)

La Rioja, , Argentina

Site Status

CEDIT

Salta, , Argentina

Site Status

Centro Medico San Roque S.R.L.

San Miguel de Tucumán, , Argentina

Site Status

Fundacion ARS Medica

San Salvador de Jujuy, , Argentina

Site Status

Blacktown Hospital - PARENT

Blacktown, , Australia

Site Status

Monash Health

Clayton, , Australia

Site Status

Epworth Freemasons

Melbourne, , Australia

Site Status

Icon Cancer Care South Brisbane

South Brisbane, , Australia

Site Status

Hospital de Câncer de Barretos - Fundação Pio XII

Barretos, , Brazil

Site Status

INCA - Instituto Nacional de Câncer

Rio de Janeiro, , Brazil

Site Status

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, , Brazil

Site Status

Fundação Faculdade Regional de Medicina de São José do Rio Preto

Sao Jose Rio Preto, , Brazil

Site Status

A. C. Camargo Cancer Center

São Paulo, , Brazil

Site Status

ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira

São Paulo, , Brazil

Site Status

IC la serena Research

La Serena, , Chile

Site Status

Centro de Investigación Clínica Bradford Hill

Santiago, , Chile

Site Status

Hospital Clínico Universidad de Chile

Santiago, , Chile

Site Status

Prosalud

Santiago, , Chile

Site Status

Instituto Clinico Oncologico del Sur (ICOS)

Temuco, , Chile

Site Status

Beijing Cancer Hospital

Beijing, , China

Site Status

Beijing Chao Yang Hospital

Beijing, , China

Site Status

Beijing Friendship Hospital, Capital Medical University

Beijing, , China

Site Status

West China Hospital, Sichuan University

Chengdu, , China

Site Status

Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

Hangzhou, , China

Site Status

The Affiliated Hospital of Qingdao University

Qingdao, , China

Site Status

Fudan University Shanghai Cancer Hospital

Shanghai, , China

Site Status

The Second Affiliated Hospital of Soochow University

Suzhou, , China

Site Status

Tianjin Medical University Cancer Institute & Hospital

Tianjin, , China

Site Status

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

Site Status

ICO - Site Paul Papin - service d'oncologie medicale

Angers, , France

Site Status

Centre Georges François Leclerc - Oncologie Médicale

Dijon, , France

Site Status

CHU Lille - Hôpital Claude Huriez

Lille, , France

Site Status

ICO - Site René Gauducheau

Saint-Herblain, , France

Site Status

CHU de Toulouse - Hôpital Ranguei

Toulouse, , France

Site Status

Vivantes Klinikum Neukoelln - Haematologie und Onkologie

Berlin, , Germany

Site Status

Universitaetsklinikum Bonn AoeR - Medizinische Klinik I Gastroenterologie

Bonn, , Germany

Site Status

Universitaetsklinikum Carl Gustav Carus TU Dresden - Medizinische Klinik I

Dresden, , Germany

Site Status

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, , Germany

Site Status

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - Medizinische Klinik I - HCC Ambulanz

Mainz, , Germany

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori Milano

Milan, , Italy

Site Status

IOV - Istituto Oncologico Veneto IRCCS - S.Semplice Dip.Oncologia dei Melanomi

Padua, , Italy

Site Status

Università Campus Bio-Medico di Roma

Roma, , Italy

Site Status

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) - UOC Oncologia

Verona, , Italy

Site Status

Chiba Cancer Center

Chiba, , Japan

Site Status

National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology

Chūōku, , Japan

Site Status

NHO Kyushu Cancer Center - Dept of Gastroenterology/Hepatology/Pancreatology

Fukuoka, , Japan

Site Status

National Cancer Center Hospital East

Kashiwa-shi, , Japan

Site Status

Cancer Institute Hospital of JFCR - Dept of Hepato,Biliary and Pancreatic Medicine

Kōtoku, , Japan

Site Status

Kyorin University Hospital

Mitaka-shi, , Japan

Site Status

Aichi Cancer Center Hospital

Nagoya, , Japan

Site Status

Osaka City University Hospital

Osaka, , Japan

Site Status

Kindai University Hospital

Osakasayama-shi, , Japan

Site Status

Kanagawa Cancer Center

Yokohama, , Japan

Site Status

Centrum Onkologii-Instytut im.M.Sklodowskiej Curie

Gliwice, , Poland

Site Status

Pratia

Krakow, , Poland

Site Status

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, , Poland

Site Status

ETG Zamosc

Zamość, , Poland

Site Status

Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)

Daejeon, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Korea University Guro Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron - Dept of Oncology

Barcelona, , Spain

Site Status

Hospital San Pedro de Alcantara - Servicio de Oncologia

Cáceres, , Spain

Site Status

Hospital Universitario Reina Sofia - Dept of Oncology

Córdoba, , Spain

Site Status

ICO l´Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, , Spain

Site Status

Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica

Madrid, , Spain

Site Status

Hospital Universitario Clinico San Carlos - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica

Valencia, , Spain

Site Status

Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica

Valencia, , Spain

Site Status

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital, Linkou

Taoyuan District, , Taiwan

Site Status

The Christie - Dept of Oncology

Manchester, , United Kingdom

Site Status

Countries

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United States Argentina Australia Brazil Chile China France Germany Italy Japan Poland South Korea Spain Taiwan United Kingdom

References

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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.

Reference Type RESULT
PMID: 32461347 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2019-001992-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200647_0055

Identifier Type: -

Identifier Source: org_study_id

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