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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001992-35 | EudraCT Number |
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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.
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| Name | Class |
|---|---|
| Merck KGaA, Darmstadt, Germany | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | Experimental |
| |
| Double-blinded Part: M7824 + Gemcitabine + Cisplatin | Experimental |
| |
| Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| M7824 | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ironwood Cancer & Research Centers - Chandler II | Chandler | Arizona | 85224 | United States | ||
| Banner MD Anderson Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32461347 | Result | 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. |
| Label | URL |
|---|---|
| Trial Awareness and Transparency website | View source |
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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
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.
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.
This study was conducted in 2 parts: Safety run-in part and double-blind part. Participants who enrolled in safety run-in part of study were not eligible to participate in double-blind part.
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| ID | Title | Description |
|---|---|---|
| FG000 | Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | 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-specified 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 14, 2021 | May 16, 2022 |
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|
| Placebo | 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 | 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 | 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). |
|
| 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 | 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. | 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) | 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. | 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) | 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. | 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) | 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. | From first documented objective response to PD or death due to any cause, assessed up to 609 days |
| 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 | 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. | Time from first treatment assessed up to 1148 days |
| 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 | 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. | Time from first treatment up to data cutoff (assessed up to 609 days) |
| 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 | Padova | 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 | Taiwan |
| The Christie - Dept of Oncology | Manchester | United Kingdom |
| US Medical Information website, Medical Resources | View source |
| FG001 | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | 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, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. |
| FG002 | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. |
| Treated |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | 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-specified 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. |
| BG001 | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | 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, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. |
| BG002 | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The DLT analysis set included all participants who experienced at least one DLT (either by Investigator or by Safety Monitoring Committee (SMC) or who completed the safety run-in, that is the 21-day DLT evaluation period, receiving at least one infusion of M7824 and of both gemcitabine and cisplatin and not being withdrawn during the DLT evaluation period for reasons other than toxicity. | Posted | Count of Participants | Participants | Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days) |
|
|
| ||||||||||||||||||||||||||
| Primary | 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. | Intent-to-Treat analysis set included all randomized participants. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Median | Full Range | Months | Time from study day 1 up to data cutoff (assessed up to 609 days) |
| |||||||||||||||||||||||||||
| Secondary | 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 | 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. | The safety run-in (SRI) analysis set includes all participants from the safety run-in part who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | Time from first treatment up to data cutoff (assessed up to 609 days) |
| ||||||||||||||||||||||||||||
| Secondary | Safety Run-in Part: Number of Participants With Grade Greater Than or Equal (>=) 3 Laboratory Abnormalities | 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. | The safety run-in (SRI) analysis set includes all participants from the safety run-in part who were administered any dose of any study intervention. | Posted | Count of Participants | Participants | Time from first treatment up to data cutoff (assessed up to 609 days) |
| ||||||||||||||||||||||||||||
| Secondary | 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) | 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. | The intent-to-treat (ITT) analysis set includes all randomized participants. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | Time from randomization of study drug until the first documentation of PD or death, assessed up to 609 days |
| |||||||||||||||||||||||||||
| Secondary | 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) | 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. | The intent-to-treat (ITT) analysis set includes all randomized participants. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | Percentage of participants | Time from randomization of study drug up to data cut off (assessed up to 609 days) |
| |||||||||||||||||||||||||||
| Secondary | 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) | 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. | The intent-to-treat (ITT) analysis set includes all randomized participants. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Median | Full Range | Months | From first documented objective response to PD or death due to any cause, assessed up to 609 days |
| |||||||||||||||||||||||||||
| Secondary | 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 | 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. | 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. Subsequently, the data for this outcome measure was not collected and analyzed. | Posted | Time from first treatment assessed up to 1148 days |
| ||||||||||||||||||||||||||||||
| Secondary | 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 | 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 analysis set included all participants who were administered at least one dose of any study treatment (M7824, placebo, gemcitabine or cisplatin). | Posted | Count of Participants | Participants | Time from first treatment up to data cutoff (assessed up to 609 days) |
|
Time from first treatment up to data cutoff (assessed up to 609 days)
Safety Run-In Part: The safety run-in (SRI) analysis set includes all participants from the safety run-in part who were administered any dose of any study intervention and double-blinded part safety analysis set included all randomized participants who were administered at least one dose of study treatment (M7824, Placebo, Gemcitabine or Cisplatin).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | 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-specified 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. | 7 | 12 | 5 | 12 | 12 | 12 |
| EG001 | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | 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, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. | 26 | 149 | 36 | 149 | 142 | 149 |
| EG002 | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. | 31 | 146 | 58 | 146 | 134 | 146 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypophysitis | Endocrine disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypopituitarism | Endocrine disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Ulcerative keratitis | Eye disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Gastric stenosis | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Gastrointestinal vascular malformation haemorrhagic | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Obstruction gastric | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Death | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hernia | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Biliary obstruction | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Immune-mediated hepatitis | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Anaphylactic shock | Immune system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Abdominal infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Biliary sepsis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Biliary tract infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Diarrhoea infectious | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Herpes simplex encephalitis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Klebsiella infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Liver abscess | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pseudomonas infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Vascular device infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Incisional hernia | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Traumatic intracranial haemorrhage | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Ischaemic cerebral infarction | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Device occlusion | Product Issues | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pelvic venous thrombosis | Vascular disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Ear congestion | Ear and labyrinth disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Ear discomfort | Ear and labyrinth disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Retinal haemorrhage | Eye disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Generalised oedema | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Systemic candida | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blood magnesium decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Iron binding capacity total decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Taste disorder | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Adjustment disorder | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pigmentation disorder | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
Data collection and analysis of Pharmacokinetics and Immunogenicity were omitted and not conducted due to business reason.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 1, 2022 | May 16, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001661 | Biliary Tract Neoplasms |
| D018281 | Cholangiocarcinoma |
| D005706 | Gallbladder Neoplasms |
| D003966 | Camurati-Engelmann Syndrome |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001660 | Biliary Tract Diseases |
| D004066 | Digestive System Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D005705 | Gallbladder Diseases |
| D010009 | Osteochondrodysplasias |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| D000093542 | Gemcitabine |
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| OG001 | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. |
|
|
| OG001 | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. |
|
|
| OG001 | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. |
|
|
| OG001 |
| Double-blinded Part: M7824 + Gemcitabine + Cisplatin |
Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. |
|
| OG001 | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 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. In case of any missed dose for chemotherapy, gemcitabine and cisplatin combination administered on Day 15 of that cycle or at the end of the scheduled 8 cycles (up to 16 administrations of gemcitabine and cisplatin combination). The administration of the missed dose on Day 15 or at the end of 8 cycles is Investigator's clinical decision. |
|
|