Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC
- Conditions
- CholangiocarcinomaGallbladder CancerBiliary Tract Cancer
- Interventions
- Registration Number
- NCT04066491
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 309
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Double-blinded Part: M7824 + Gemcitabine + Cisplatin M7824 - Double-blinded Part: Placebo + Gemcitabine + Cisplatin Gemcitabine - Double-blinded Part: Placebo + Gemcitabine + Cisplatin Placebo - Safety Run-In Part: M7824 + Gemcitabine + Cisplatin M7824 - Double-blinded Part: Placebo + Gemcitabine + Cisplatin Cisplatin - Safety Run-In Part: M7824 + Gemcitabine + Cisplatin Cisplatin - Safety Run-In Part: M7824 + Gemcitabine + Cisplatin Gemcitabine - Double-blinded Part: M7824 + Gemcitabine + Cisplatin Cisplatin - Double-blinded Part: M7824 + Gemcitabine + Cisplatin Gemcitabine -
- Primary Outcome Measures
Name Time Method Safety Run-in Part: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days) 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.
Double-blind Part: Overall Survival Time from study day 1 up to data cutoff (assessed up to 609 days) 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.
- Secondary Outcome Measures
Name Time Method 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 Progression free survival was defined as the time from randomization of study intervention until the first documentation of disease progression (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
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) Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on treatment period. TEAEs included serious TEAEs and non-serious TEAEs.
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 Time from first treatment up to data cutoff (assessed up to 609 days) AE was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on treatment period. TEAEs included serious TEAEs and non-serious TEAEs. Adverse events of special interest (AESI) are serious or non-serious AEs that are of clinical interest and should be closely followed. For this study, AESIs include the following: Infusion-related reactions including immediate hypersensitivity; Immune-related AEs; Transforming growth factor beta (TGFβ) inhibition mediated skin reactions; Anemia; Bleeding AEs.
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) Laboratory investigation included hematology and biochemistry. The number of participants with Grade \>=3 laboratory abnormalities were reported. Severity of grade 3 or higher TEAEs were graded using NCI-CTCAE v5.0 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death.
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) Percentage of participants with confirmed objective response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC.
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 DOR was defined for participants with objective response, as the time from first documentation of objective response (confirmed Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.
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 Time from first treatment assessed up to 1148 days Durable Response was defined as the number of participants with confirmed objective response (CR or PR) according to RECIST 1.1, determined by Investigator with duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions.
Trial Locations
- Locations (99)
Methodist Transplant Physicians
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center - Unit 429
🇺🇸Houston, Texas, United States
Renovatio Clinical - CENTRAL SITE
🇺🇸The Woodlands, Texas, United States
West China Hospital, Sichuan University
🇨🇳Chengdu, China
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Japan
Kyorin University Hospital
🇯🇵Mitaka-shi, Japan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Ironwood Cancer & Research Centers - Chandler II
🇺🇸Chandler, Arizona, United States
Fundacion ARS Medica
🇦🇷San Salvador de Jujuy, Argentina
Centro Oncologico Riojano Integral (CORI)
🇦🇷La Rioja, Argentina
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Sidney Kimmel Comprehensive Cancer Center at John Hopkins
🇺🇸Baltimore, Maryland, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Instituto de Investigaciones Metabolicas (IDIM)
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, China
Centre Georges François Leclerc - Oncologie Médicale
🇫🇷Dijon cedex, France
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Pratia
🇵🇱Krakow, Poland
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
University of Kansas Medical Center Research Institute, Inc. - University of Kansas Cancer Center/Bloch Pavilion
🇺🇸Westwood, Kansas, United States
CEDIT
🇦🇷Salta, Argentina
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Mayo Clinic in Florida - Department of Neurology
🇺🇸Jacksonville, Florida, United States
Instituto Medico Especializado Alexander Fleming
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Centro Medico San Roque S.R.L.
🇦🇷San Miguel de Tucuman, Argentina
Blacktown Hospital - PARENT
🇦🇺Blacktown, Australia
Epworth Freemasons
🇦🇺Melbourne, Australia
Monash Health
🇦🇺Clayton, 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
Beijing Chao Yang Hospital
🇨🇳Beijing, China
Fundação Faculdade Regional de Medicina de São José do Rio Preto
🇧🇷Sao Jose Rio Preto, Brazil
A. C. Camargo Cancer Center
🇧🇷São Paulo, Brazil
IC la serena Research
🇨🇱La Serena, Chile
ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira
🇧🇷São Paulo, Brazil
Prosalud
🇨🇱Santiago, Chile
Centro de Investigación Clínica Bradford Hill
🇨🇱Santiago, Chile
Instituto Clinico Oncologico del Sur (ICOS)
🇨🇱Temuco, Chile
Beijing Cancer Hospital
🇨🇳Beijing, China
Hospital Clínico Universidad de Chile
🇨🇱Santiago, Chile
Fudan University Shanghai Cancer Hospital
🇨🇳Shanghai, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, China
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
🇨🇳Hangzhou, 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
CHU Lille - Hôpital Claude Huriez
🇫🇷Lille cedex, France
ICO - Site Paul Papin - service d'oncologie medicale
🇫🇷Angers Cedex 2, France
ICO - Site René Gauducheau
🇫🇷Saint Herblain, France
Vivantes Klinikum Neukoelln - Haematologie und Onkologie
🇩🇪Berlin, Germany
CHU de Toulouse - Hôpital Ranguei
🇫🇷Toulouse Cedex 9, France
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
🇮🇹Milano, Italy
IOV - Istituto Oncologico Veneto IRCCS - S.Semplice Dip.Oncologia dei Melanomi
🇮🇹Padova, Italy
Università Campus Bio-Medico di Roma
🇮🇹Roma, Italy
Chiba Cancer Center
🇯🇵Chiba-shi, Japan
Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) - UOC Oncologia
🇮🇹Verona, Italy
NHO Kyushu Cancer Center - Dept of Gastroenterology/Hepatology/Pancreatology
🇯🇵Fukuoka-shi, Japan
National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology
🇯🇵Chuo-ku, Japan
Cancer Institute Hospital of JFCR - Dept of Hepato,Biliary and Pancreatic Medicine
🇯🇵Koto-ku, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya-shi, Japan
Kanagawa Cancer Center
🇯🇵Yokohama-shi, Japan
Osaka City University Hospital
🇯🇵Osaka-shi, Japan
Kindai University Hospital
🇯🇵Osakasayama-shi, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
🇰🇷Daejeon, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
🇵🇱Gliwice, Poland
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hospital San Pedro de Alcantara - Servicio de Oncologia
🇪🇸Caceres, Spain
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
🇵🇱Warszawa, Poland
ETG Zamosc
🇵🇱Zamosc, Poland
Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron - Dept of Oncology
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
🇪🇸Madrid, Spain
ICO l´Hospitalet - Hospital Duran i Reynals
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital Universitario Reina Sofia - Dept of Oncology
🇪🇸Cordoba, 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
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
The Christie - Dept of Oncology
🇬🇧Manchester, United Kingdom
Related News
Triplet combination of durvalumab, tremelimumab, and ...
- Prev
- 1
- Next