Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2/Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Safety Run-In Part: M7824 + Gemcitabine + Cisplatin
|
Drug: 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.
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).
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).
|
Experimental: Double-blinded Part: M7824 + Gemcitabine + Cisplatin
|
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).
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).
|
Placebo Comparator: Double-blinded Part: Placebo + Gemcitabine + Cisplatin
|
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.
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).
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).
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 to 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.
- Safety Run-in Part: Number of Participants With Grade Greater Than or Equal (>=) 3 Laboratory Abnormalities [Time from first treatment to 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: 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 approximately 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.
- 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 approximately 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.
- Durable Response of at Least 6 Months According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 [Time from first treatment assessed up to 1199 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 [Time from first treatment to 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Are participants with histologically or cytologically confirmed locally advanced or metastatic BTC
-
Participants must have available tumor tissue (primary or metastatic) (archival or fresh biopsies) before the first administration of study treatment
-
At least 1 measurable lesion according to RECIST 1.1
-
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study entry and at Week 1, Day 1 prior to dosing
-
Life expectancy of >= 12 weeks, as judged by the Investigator
-
Adequate hematological function, hepatic function, renal function, coagulation function as defined in the protocol
-
Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals
-
Other protocol defined inclusion criteria could apply
Exclusion Criteria:
-
Previous and/or intercurrent cancers
-
Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression
-
Participants with symptomatic central nervous system (CNS) metastases
-
Significant acute or chronic infection including known history of positive test for human immunodeficiency virus (HIV), active tuberculosis, uncontrolled biliary infection and active bacterial or fungal infection requiring systemic therapy (with the exception of hepatitis B and hepatitis C) requiring systemic therapy at study entry and at Week 1 Day 1 prior to dosing.
-
Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
-
History of or concurrent interstitial lung disease
-
History of hypersensitivity reactions to bintrafusp alfa, anaphylaxis, or recent (within 5 months) uncontrolled asthma, cardiovascular/cerebrovascular disease
-
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before randomization
-
Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints)
-
Other protocol defined exclusion criteria could apply
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Ironwood Cancer & Research Centers - Chandler II | Chandler | Arizona | United States | 85224 |
2 | Banner MD Anderson Cancer Center | Gilbert | Arizona | United States | 85234 |
3 | Mayo Clinic Arizona | Phoenix | Arizona | United States | 85054 |
4 | Beverly Hills Cancer Center | Beverly Hills | California | United States | 90211 |
5 | Mayo Clinic in Florida - Department of Neurology | Jacksonville | Florida | United States | 32224 |
6 | Mount Sinai Medical Center | Miami Beach | Florida | United States | 33140 |
7 | University of Kansas Medical Center Research Institute, Inc. - University of Kansas Cancer Center/Bloch Pavilion | Westwood | Kansas | United States | 66216 |
8 | Sidney Kimmel Comprehensive Cancer Center at John Hopkins | Baltimore | Maryland | United States | 21287 |
9 | Mayo Clinic - Rochester | Rochester | Minnesota | United States | 55905 |
10 | Methodist Transplant Physicians | Dallas | Texas | United States | 75203 |
11 | MD Anderson Cancer Center - Unit 429 | Houston | Texas | United States | 77030 |
12 | Renovatio Clinical - CENTRAL SITE | The Woodlands | Texas | United States | 77380 |
13 | Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo | Ciudad Autonoma Buenos Aires | Argentina | ||
14 | Instituto de Investigaciones Metabolicas (IDIM) | Ciudad Autonoma Buenos Aires | Argentina | ||
15 | Instituto Medico Especializado Alexander Fleming | Ciudad Autonoma Buenos Aires | Argentina | ||
16 | Centro Oncologico Riojano Integral (CORI) | La Rioja | Argentina | ||
17 | CEDIT | Salta | Argentina | ||
18 | Centro Medico San Roque S.R.L. | San Miguel de Tucuman | Argentina | ||
19 | Fundacion ARS Medica | San Salvador de Jujuy | Argentina | ||
20 | Blacktown Hospital - PARENT | Blacktown | Australia | ||
21 | Monash Health | Clayton | Australia | ||
22 | Epworth Freemasons | Melbourne | Australia | ||
23 | Icon Cancer Care South Brisbane | South Brisbane | Australia | ||
24 | INCA - Instituto Nacional de Câncer | Rio de Janeiro | Brazil | ||
25 | CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia | Santo André | Brazil | ||
26 | Fundação Faculdade Regional de Medicina de São José do Rio Preto | Sao Jose Rio Preto | Brazil | ||
27 | A. C. Camargo Cancer Center | São Paulo | Brazil | ||
28 | ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira | São Paulo | Brazil | ||
29 | IC la serena Research | La Serena | Chile | ||
30 | Centro de Investigación Clínica Bradford Hill | Santiago | Chile | ||
31 | Hospital Clínico Universidad de Chile | Santiago | Chile | ||
32 | Prosalud | Santiago | Chile | ||
33 | Instituto Clinico Oncologico del Sur (ICOS) | Temuco | Chile | ||
34 | Beijing Cancer Hospital | Beijing | China | ||
35 | Beijing Friendship Hospital, Capital Medical University | Beijing | China | ||
36 | West China Hospital, Sichuan University | Chengdu | China | ||
37 | Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine | Hangzhou | China | ||
38 | The Affiliated Hospital of Qingdao University | Qingdao | China | ||
39 | Fudan University Shanghai Cancer Hospital | Shanghai | China | ||
40 | The Second Affiliated Hospital of Soochow University | Suzhou | China | ||
41 | Tianjin Medical University Cancer Institute & Hospital | Tianjin | China | ||
42 | Union Hospital Tongji Medical College Huazhong University of Science and Technology | Wuhan | China | ||
43 | ICO - Site Paul Papin - service d'oncologie medicale | Angers Cedex 2 | France | ||
44 | Centre Georges François Leclerc - Oncologie Médicale | Dijon cedex | France | ||
45 | CHU Lille - Hôpital Claude Huriez | Lille cedex | France | ||
46 | ICO - Site René Gauducheau | Saint Herblain | France | ||
47 | CHU de Toulouse - Hôpital Ranguei | Toulouse Cedex 9 | France | ||
48 | Vivantes Klinikum Neukoelln - Haematologie und Onkologie | Berlin | Germany | ||
49 | Universitaetsklinikum Bonn AoeR - Medizinische Klinik I Gastroenterologie | Bonn | Germany | ||
50 | Universitaetsklinikum Carl Gustav Carus TU Dresden - Medizinische Klinik I | Dresden | Germany | ||
51 | Klinikum der Johann Wolfgang Goethe-Universitaet | Frankfurt | Germany | ||
52 | Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - Medizinische Klinik I - HCC Ambulanz | Mainz | Germany | ||
53 | Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) - UOC Oncologia | Verona | Italy | ||
54 | Chiba Cancer Center | Chiba-shi | Japan | ||
55 | National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology | Chuo-ku | Japan | ||
56 | NHO Kyushu Cancer Center - Dept of Gastroenterology/Hepatology/Pancreatology | Fukuoka-shi | Japan | ||
57 | National Cancer Center Hospital East | Kashiwa-shi | Japan | ||
58 | Cancer Institute Hospital of JFCR - Dept of Hepato,Biliary and Pancreatic Medicine | Koto-ku | Japan | ||
59 | Kyorin University Hospital | Mitaka-shi | Japan | ||
60 | Aichi Cancer Center Hospital | Nagoya-shi | Japan | ||
61 | Osaka City University Hospital | Osaka-shi | Japan | ||
62 | Kindai University Hospital | Osakasayama-shi | Japan | ||
63 | Kanagawa Cancer Center | Yokohama-shi | Japan | ||
64 | Chungnam National University Hospital - Department of Internal Medicine (Rheumatology) | Daejeon | Korea, Republic of | ||
65 | Seoul National University Bundang Hospital | Seongnam-si | Korea, Republic of | ||
66 | Asan Medical Center | Seoul | Korea, Republic of | ||
67 | Korea University Anam Hospital | Seoul | Korea, Republic of | ||
68 | Korea University Guro Hospital | Seoul | Korea, Republic of | ||
69 | Samsung Medical Center | Seoul | Korea, Republic of | ||
70 | Seoul National University Hospital | Seoul | Korea, Republic of | ||
71 | Severance Hospital, Yonsei University Health System | Seoul | Korea, Republic of | ||
72 | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | Korea, Republic of | ||
73 | Centrum Onkologii-Instytut im.M.Sklodowskiej Curie | Gliwice | Poland | ||
74 | Pratia | Krakow | Poland | ||
75 | Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy | Warszawa | Poland | ||
76 | ETG Zamosc | Zamosc | Poland | ||
77 | Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia | Barcelona | Spain | ||
78 | Hospital Universitari Vall d'Hebron - Dept of Oncology | Barcelona | Spain | ||
79 | Hospital San Pedro de Alcantara - Servicio de Oncologia | Caceres | Spain | ||
80 | Hospital Universitario Reina Sofia - Dept of Oncology | Cordoba | Spain | ||
81 | ICO l´Hospitalet - Hospital Duran i Reynals | L'Hospitalet de Llobregat | Spain | ||
82 | Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica | Madrid | Spain | ||
83 | Hospital Universitario Clinico San Carlos - Servicio de Oncologia | Madrid | Spain | ||
84 | Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia | Madrid | Spain | ||
85 | Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica | Valencia | Spain | ||
86 | Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica | Valencia | Spain | ||
87 | Kaohsiung Chang Gung Memorial Hospital | Kaohsiung | Taiwan | ||
88 | China Medical University Hospital | Taichung | Taiwan | ||
89 | Taichung Veterans General Hospital | Taichung | Taiwan | ||
90 | National Cheng Kung University Hospital | Tainan | Taiwan | ||
91 | National Taiwan University Hospital | Taipei | Taiwan | ||
92 | Taipei Veterans General Hospital | Taipei | Taiwan | ||
93 | Chang Gung Memorial Hospital, Linkou | Taoyuan | Taiwan | ||
94 | The Christie - Dept of Oncology | Manchester | United Kingdom |
Sponsors and Collaborators
- EMD Serono Research & Development Institute, Inc.
- Merck KGaA, Darmstadt, Germany
Investigators
- Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- MS200647_0055
- 2019-001992-35
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | First participant signed informed consent: 20-Sep-2019, Primary Analysis cutoff date: 20-May-2021. |
Arm/Group Title | Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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. |
Period Title: Overall Study | |||
STARTED | 12 | 149 | 148 |
Treated | 12 | 149 | 146 |
COMPLETED | 8 | 38 | 39 |
NOT COMPLETED | 4 | 111 | 109 |
Baseline Characteristics
Arm/Group Title | Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | Total |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
Overall Participants | 12 | 149 | 148 | 309 |
Age (Years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [Years] |
66
(11.9)
|
64
(10.6)
|
63
(10.8)
|
63
(10.7)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
5
41.7%
|
78
52.3%
|
68
45.9%
|
151
48.9%
|
Male |
7
58.3%
|
71
47.7%
|
80
54.1%
|
158
51.1%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
1
8.3%
|
21
14.1%
|
22
14.9%
|
44
14.2%
|
Not Hispanic or Latino |
11
91.7%
|
128
85.9%
|
126
85.1%
|
265
85.8%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | ||||
American Indian or Alaska Native |
0
0%
|
1
0.7%
|
0
0%
|
1
0.3%
|
Asian |
6
50%
|
93
62.4%
|
90
60.8%
|
189
61.2%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.7%
|
0
0%
|
1
0.3%
|
Black or African American |
0
0%
|
0
0%
|
1
0.7%
|
1
0.3%
|
White |
6
50%
|
51
34.2%
|
51
34.5%
|
108
35%
|
More than one race |
0
0%
|
0
0%
|
1
0.7%
|
1
0.3%
|
Unknown or Not Reported |
0
0%
|
3
2%
|
5
3.4%
|
8
2.6%
|
Outcome Measures
Title | Safety Run-in Part: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) |
---|---|
Description | 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. |
Time Frame | Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Safety Run-In Part: M7824 + Gemcitabine + Cisplatin |
---|---|
Arm/Group Description | 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 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 Participants | 12 |
Count of Participants [Participants] |
0
0%
|
Title | Double-blind Part: Overall Survival |
---|---|
Description | 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 Frame | Time from study day 1 up to data cutoff (assessed up to 609 days) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 18 | 23 |
Median (Full Range) [Months] |
11.5
|
11.5
|
Title | 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 |
---|---|
Description | 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. |
Time Frame | Time from first treatment to up to data cutoff (assessed up to 609 days) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Safety Run-In Part: M7824 + Gemcitabine + Cisplatin |
---|---|
Arm/Group Description | 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 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 Participants | 12 |
Participants with TEAEs |
12
100%
|
Participants with Serious TEAEs |
5
41.7%
|
Participants with Treatment-related TEAEs |
11
91.7%
|
Title | Safety Run-in Part: Number of Participants With Grade Greater Than or Equal (>=) 3 Laboratory Abnormalities |
---|---|
Description | 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 Frame | Time from first treatment to up to data cutoff (assessed up to 609 days) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Safety Run-In Part: M7824 + Gemcitabine + Cisplatin |
---|---|
Arm/Group Description | 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 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. |
Measure Participants | 12 |
Hemoglobin low |
6
50%
|
Leukocytes low |
4
33.3%
|
Neutrophils low |
6
50%
|
Platelets low |
3
25%
|
Alanine Aminotransferase high |
2
16.7%
|
Bilirubin high |
1
8.3%
|
Creatinine high |
1
8.3%
|
Lipase high |
1
8.3%
|
Potassium low |
1
8.3%
|
Lymphocytes low |
2
16.7%
|
Corrected Calcium high |
1
8.3%
|
Title | 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) |
---|---|
Description | 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 Frame | Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 609 days |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 44 | 49 |
Median (95% Confidence Interval) [Months] |
5.6
|
5.5
|
Title | 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) |
---|---|
Description | 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 Frame | Time from randomization of study drug up to data cut off (assessed up to 609 days) |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 77 | 73 |
Number (95% Confidence Interval) [Percentage of participants] |
19.5
162.5%
|
31.5
21.1%
|
Title | 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) |
---|---|
Description | 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. |
Time Frame | From first documented objective response to PD or death due to any cause, assessed approximately up to 609 days |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 7 | 9 |
Median (Full Range) [Months] |
12.5
|
7.0
|
Title | Durable Response of at Least 6 Months According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 |
---|---|
Description | |
Time Frame | Time from first treatment assessed up to 1199 days |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | 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 |
---|---|
Description | 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 Frame | Time from first treatment to up to data cutoff (assessed up to 609 days) |
Outcome Measure Data
Analysis Population Description |
---|
Safety analysis set included all participants who were administered at least one dose of any study treatment (M7824, placebo, gemcitabine or cisplatin). |
Arm/Group Title | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin |
---|---|---|
Arm/Group Description | 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. | 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. |
Measure Participants | 149 | 146 |
Participants with TEAEs |
145
1208.3%
|
140
94%
|
Participants with Serious TEAEs |
36
300%
|
58
38.9%
|
Participants with Treatment-related TEAEs |
136
1133.3%
|
133
89.3%
|
Participants with AESIs |
8
66.7%
|
16
10.7%
|
Adverse Events
Time Frame | Time from first treatment to up to data cutoff (assessed up to 609 days) | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | 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). | |||||
Arm/Group Title | Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | |||
Arm/Group Description | 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. | 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. | 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. | |||
All Cause Mortality |
||||||
Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 7/12 (58.3%) | 26/149 (17.4%) | 31/146 (21.2%) | |||
Serious Adverse Events |
||||||
Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/12 (41.7%) | 36/149 (24.2%) | 58/146 (39.7%) | |||
Blood and lymphatic system disorders | ||||||
Anaemia | 0/12 (0%) | 2/149 (1.3%) | 7/146 (4.8%) | |||
Febrile neutropenia | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Neutropenia | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Pancytopenia | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Thrombocytopenia | 1/12 (8.3%) | 2/149 (1.3%) | 0/146 (0%) | |||
Cardiac disorders | ||||||
Cardiac arrest | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Endocrine disorders | ||||||
Adrenal insufficiency | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Hypophysitis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Hypopituitarism | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Hypothyroidism | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Eye disorders | ||||||
Ulcerative keratitis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Gastrointestinal disorders | ||||||
Abdominal pain | 0/12 (0%) | 1/149 (0.7%) | 1/146 (0.7%) | |||
Abdominal pain upper | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Ascites | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Colitis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Duodenal ulcer haemorrhage | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Gastric haemorrhage | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Gastric stenosis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Gastric ulcer | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Gastrointestinal haemorrhage | 1/12 (8.3%) | 1/149 (0.7%) | 2/146 (1.4%) | |||
Gastrointestinal vascular malformation haemorrhagic | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Haematochezia | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Intestinal obstruction | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Lower gastrointestinal haemorrhage | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Nausea | 0/12 (0%) | 0/149 (0%) | 3/146 (2.1%) | |||
Obstruction gastric | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Pancreatitis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Rectal haemorrhage | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Upper gastrointestinal haemorrhage | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Vomiting | 0/12 (0%) | 0/149 (0%) | 3/146 (2.1%) | |||
General disorders | ||||||
Asthenia | 1/12 (8.3%) | 0/149 (0%) | 1/146 (0.7%) | |||
Chills | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Death | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Disease progression | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Fatigue | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Hernia | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Malaise | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Oedema peripheral | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Pyrexia | 1/12 (8.3%) | 2/149 (1.3%) | 4/146 (2.7%) | |||
Hepatobiliary disorders | ||||||
Bile duct stenosis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Bile duct stone | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Biliary obstruction | 1/12 (8.3%) | 3/149 (2%) | 1/146 (0.7%) | |||
Cholangitis | 0/12 (0%) | 5/149 (3.4%) | 6/146 (4.1%) | |||
Cholecystitis | 1/12 (8.3%) | 1/149 (0.7%) | 1/146 (0.7%) | |||
Cholestasis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Hepatic failure | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Immune-mediated hepatitis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Jaundice cholestatic | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Immune system disorders | ||||||
Anaphylactic shock | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Infections and infestations | ||||||
Abdominal infection | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Bacteraemia | 0/12 (0%) | 0/149 (0%) | 2/146 (1.4%) | |||
Biliary sepsis | 0/12 (0%) | 0/149 (0%) | 2/146 (1.4%) | |||
Biliary tract infection | 0/12 (0%) | 3/149 (2%) | 2/146 (1.4%) | |||
COVID-19 | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Diarrhoea infectious | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Herpes simplex encephalitis | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Klebsiella infection | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Liver abscess | 0/12 (0%) | 2/149 (1.3%) | 1/146 (0.7%) | |||
Pneumonia | 0/12 (0%) | 1/149 (0.7%) | 1/146 (0.7%) | |||
Pseudomonas infection | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Sepsis | 0/12 (0%) | 0/149 (0%) | 2/146 (1.4%) | |||
Soft tissue infection | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Urinary tract infection | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Vascular device infection | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Injury, poisoning and procedural complications | ||||||
Incisional hernia | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Infusion related reaction | 0/12 (0%) | 0/149 (0%) | 3/146 (2.1%) | |||
Traumatic intracranial haemorrhage | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Investigations | ||||||
Alanine aminotransferase increased | 0/12 (0%) | 0/149 (0%) | 2/146 (1.4%) | |||
Blood albumin decreased | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Blood bilirubin increased | 0/12 (0%) | 3/149 (2%) | 2/146 (1.4%) | |||
Blood sodium decreased | 0/12 (0%) | 1/149 (0.7%) | 1/146 (0.7%) | |||
Lipase increased | 0/12 (0%) | 1/149 (0.7%) | 1/146 (0.7%) | |||
Lymphocyte count decreased | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Neutrophil count decreased | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Platelet count decreased | 0/12 (0%) | 2/149 (1.3%) | 1/146 (0.7%) | |||
Transaminases increased | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Metabolism and nutrition disorders | ||||||
Decreased appetite | 0/12 (0%) | 0/149 (0%) | 2/146 (1.4%) | |||
Dehydration | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Hypomagnesaemia | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Hyponatraemia | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Bone pain | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Cancer pain | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Metastases to bone | 0/12 (0%) | 2/149 (1.3%) | 0/146 (0%) | |||
Squamous cell carcinoma | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Squamous cell carcinoma of skin | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Tumour associated fever | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Nervous system disorders | ||||||
Cerebral infarction | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Cerebral ischaemia | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Encephalopathy | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Facial paralysis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Haemorrhage intracranial | 0/12 (0%) | 0/149 (0%) | 2/146 (1.4%) | |||
Ischaemic cerebral infarction | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Product Issues | ||||||
Device occlusion | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Renal and urinary disorders | ||||||
Acute kidney injury | 1/12 (8.3%) | 0/149 (0%) | 2/146 (1.4%) | |||
Dysuria | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Haematuria | 0/12 (0%) | 1/149 (0.7%) | 1/146 (0.7%) | |||
Renal failure | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Tubulointerstitial nephritis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Epistaxis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Pleural effusion | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Respiratory distress | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Respiratory failure | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Skin and subcutaneous tissue disorders | ||||||
Dermatitis | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Erythema multiforme | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Urticaria | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Vascular disorders | ||||||
Embolism | 0/12 (0%) | 0/149 (0%) | 2/146 (1.4%) | |||
Hypertension | 0/12 (0%) | 0/149 (0%) | 1/146 (0.7%) | |||
Pelvic venous thrombosis | 0/12 (0%) | 1/149 (0.7%) | 0/146 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Safety Run-In Part: M7824 + Gemcitabine + Cisplatin | Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Double-blinded Part: M7824 + Gemcitabine + Cisplatin | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 12/12 (100%) | 142/149 (95.3%) | 134/146 (91.8%) | |||
Blood and lymphatic system disorders | ||||||
Anaemia | 6/12 (50%) | 79/149 (53%) | 78/146 (53.4%) | |||
Leukopenia | 1/12 (8.3%) | 7/149 (4.7%) | 4/146 (2.7%) | |||
Lymphopenia | 1/12 (8.3%) | 1/149 (0.7%) | 1/146 (0.7%) | |||
Neutropenia | 1/12 (8.3%) | 40/149 (26.8%) | 25/146 (17.1%) | |||
Thrombocytopenia | 1/12 (8.3%) | 12/149 (8.1%) | 14/146 (9.6%) | |||
Cardiac disorders | ||||||
Bradycardia | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Tachycardia | 1/12 (8.3%) | 1/149 (0.7%) | 0/146 (0%) | |||
Ear and labyrinth disorders | ||||||
Ear congestion | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Ear discomfort | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Tinnitus | 1/12 (8.3%) | 0/149 (0%) | 3/146 (2.1%) | |||
Eye disorders | ||||||
Eye pain | 1/12 (8.3%) | 1/149 (0.7%) | 0/146 (0%) | |||
Retinal haemorrhage | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Vision blurred | 1/12 (8.3%) | 1/149 (0.7%) | 0/146 (0%) | |||
Gastrointestinal disorders | ||||||
Abdominal distension | 1/12 (8.3%) | 3/149 (2%) | 5/146 (3.4%) | |||
Abdominal pain | 2/12 (16.7%) | 11/149 (7.4%) | 13/146 (8.9%) | |||
Abdominal pain lower | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Abdominal pain upper | 2/12 (16.7%) | 6/149 (4%) | 5/146 (3.4%) | |||
Aphthous ulcer | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Ascites | 0/12 (0%) | 9/149 (6%) | 1/146 (0.7%) | |||
Constipation | 4/12 (33.3%) | 51/149 (34.2%) | 40/146 (27.4%) | |||
Diarrhoea | 3/12 (25%) | 15/149 (10.1%) | 20/146 (13.7%) | |||
Dyspepsia | 1/12 (8.3%) | 10/149 (6.7%) | 6/146 (4.1%) | |||
Gingival bleeding | 1/12 (8.3%) | 0/149 (0%) | 13/146 (8.9%) | |||
Nausea | 6/12 (50%) | 72/149 (48.3%) | 64/146 (43.8%) | |||
Rectal haemorrhage | 1/12 (8.3%) | 1/149 (0.7%) | 1/146 (0.7%) | |||
Stomatitis | 0/12 (0%) | 6/149 (4%) | 16/146 (11%) | |||
Vomiting | 1/12 (8.3%) | 32/149 (21.5%) | 31/146 (21.2%) | |||
General disorders | ||||||
Asthenia | 2/12 (16.7%) | 18/149 (12.1%) | 23/146 (15.8%) | |||
Fatigue | 4/12 (33.3%) | 35/149 (23.5%) | 29/146 (19.9%) | |||
Generalised oedema | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Malaise | 0/12 (0%) | 11/149 (7.4%) | 5/146 (3.4%) | |||
Mucosal inflammation | 1/12 (8.3%) | 4/149 (2.7%) | 1/146 (0.7%) | |||
Oedema peripheral | 1/12 (8.3%) | 10/149 (6.7%) | 9/146 (6.2%) | |||
Pyrexia | 3/12 (25%) | 19/149 (12.8%) | 33/146 (22.6%) | |||
Hepatobiliary disorders | ||||||
Cholangitis | 1/12 (8.3%) | 3/149 (2%) | 2/146 (1.4%) | |||
Hyperbilirubinaemia | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Infections and infestations | ||||||
Clostridium difficile infection | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Cystitis | 1/12 (8.3%) | 1/149 (0.7%) | 4/146 (2.7%) | |||
Herpes zoster | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Nasopharyngitis | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Oral candidiasis | 1/12 (8.3%) | 1/149 (0.7%) | 0/146 (0%) | |||
Pneumonia | 1/12 (8.3%) | 1/149 (0.7%) | 0/146 (0%) | |||
Systemic candida | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Urinary tract infection | 0/12 (0%) | 4/149 (2.7%) | 9/146 (6.2%) | |||
Injury, poisoning and procedural complications | ||||||
Infusion related reaction | 1/12 (8.3%) | 3/149 (2%) | 6/146 (4.1%) | |||
Investigations | ||||||
Alanine aminotransferase increased | 2/12 (16.7%) | 20/149 (13.4%) | 13/146 (8.9%) | |||
Amylase increased | 2/12 (16.7%) | 8/149 (5.4%) | 4/146 (2.7%) | |||
Aspartate aminotransferase increased | 2/12 (16.7%) | 22/149 (14.8%) | 13/146 (8.9%) | |||
Blood albumin decreased | 1/12 (8.3%) | 4/149 (2.7%) | 1/146 (0.7%) | |||
Blood alkaline phosphatase increased | 1/12 (8.3%) | 8/149 (5.4%) | 7/146 (4.8%) | |||
Blood bilirubin increased | 0/12 (0%) | 14/149 (9.4%) | 9/146 (6.2%) | |||
Blood creatinine increased | 1/12 (8.3%) | 7/149 (4.7%) | 6/146 (4.1%) | |||
Blood magnesium decreased | 1/12 (8.3%) | 3/149 (2%) | 2/146 (1.4%) | |||
Creatinine renal clearance decreased | 1/12 (8.3%) | 9/149 (6%) | 4/146 (2.7%) | |||
Gamma-glutamyltransferase increased | 1/12 (8.3%) | 10/149 (6.7%) | 4/146 (2.7%) | |||
Haemoglobin decreased | 1/12 (8.3%) | 0/149 (0%) | 3/146 (2.1%) | |||
Iron binding capacity total decreased | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Lipase increased | 2/12 (16.7%) | 9/149 (6%) | 5/146 (3.4%) | |||
Neutrophil count decreased | 5/12 (41.7%) | 59/149 (39.6%) | 28/146 (19.2%) | |||
Platelet count decreased | 3/12 (25%) | 38/149 (25.5%) | 34/146 (23.3%) | |||
White blood cell count decreased | 3/12 (25%) | 36/149 (24.2%) | 19/146 (13%) | |||
Metabolism and nutrition disorders | ||||||
Decreased appetite | 3/12 (25%) | 36/149 (24.2%) | 30/146 (20.5%) | |||
Diabetes mellitus | 1/12 (8.3%) | 1/149 (0.7%) | 0/146 (0%) | |||
Hypercalcaemia | 1/12 (8.3%) | 4/149 (2.7%) | 3/146 (2.1%) | |||
Hypocalcaemia | 1/12 (8.3%) | 4/149 (2.7%) | 1/146 (0.7%) | |||
Hypokalaemia | 1/12 (8.3%) | 10/149 (6.7%) | 7/146 (4.8%) | |||
Hypomagnesaemia | 0/12 (0%) | 13/149 (8.7%) | 8/146 (5.5%) | |||
Hyponatraemia | 0/12 (0%) | 8/149 (5.4%) | 10/146 (6.8%) | |||
Hypophosphataemia | 1/12 (8.3%) | 3/149 (2%) | 1/146 (0.7%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Back pain | 1/12 (8.3%) | 6/149 (4%) | 8/146 (5.5%) | |||
Myalgia | 0/12 (0%) | 10/149 (6.7%) | 0/146 (0%) | |||
Nervous system disorders | ||||||
Dizziness | 0/12 (0%) | 13/149 (8.7%) | 8/146 (5.5%) | |||
Dysgeusia | 2/12 (16.7%) | 3/149 (2%) | 6/146 (4.1%) | |||
Headache | 0/12 (0%) | 13/149 (8.7%) | 12/146 (8.2%) | |||
Peripheral sensory neuropathy | 1/12 (8.3%) | 1/149 (0.7%) | 5/146 (3.4%) | |||
Taste disorder | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Psychiatric disorders | ||||||
Adjustment disorder | 1/12 (8.3%) | 1/149 (0.7%) | 0/146 (0%) | |||
Anxiety | 1/12 (8.3%) | 6/149 (4%) | 3/146 (2.1%) | |||
Insomnia | 1/12 (8.3%) | 2/149 (1.3%) | 12/146 (8.2%) | |||
Renal and urinary disorders | ||||||
Pollakiuria | 1/12 (8.3%) | 2/149 (1.3%) | 0/146 (0%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Cough | 3/12 (25%) | 9/149 (6%) | 3/146 (2.1%) | |||
Dyspnoea exertional | 1/12 (8.3%) | 0/149 (0%) | 3/146 (2.1%) | |||
Epistaxis | 2/12 (16.7%) | 3/149 (2%) | 19/146 (13%) | |||
Pulmonary embolism | 1/12 (8.3%) | 1/149 (0.7%) | 2/146 (1.4%) | |||
Skin and subcutaneous tissue disorders | ||||||
Alopecia | 0/12 (0%) | 16/149 (10.7%) | 5/146 (3.4%) | |||
Blister | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Dermatitis | 1/12 (8.3%) | 0/149 (0%) | 3/146 (2.1%) | |||
Erythema multiforme | 1/12 (8.3%) | 1/149 (0.7%) | 2/146 (1.4%) | |||
Palmar-plantar erythrodysaesthesia syndrome | 1/12 (8.3%) | 0/149 (0%) | 1/146 (0.7%) | |||
Pigmentation disorder | 1/12 (8.3%) | 0/149 (0%) | 0/146 (0%) | |||
Pruritus | 4/12 (33.3%) | 14/149 (9.4%) | 35/146 (24%) | |||
Rash | 6/12 (50%) | 21/149 (14.1%) | 36/146 (24.7%) | |||
Rash maculo-papular | 0/12 (0%) | 4/149 (2.7%) | 10/146 (6.8%) | |||
Rash papular | 1/12 (8.3%) | 0/149 (0%) | 1/146 (0.7%) | |||
Skin lesion | 1/12 (8.3%) | 0/149 (0%) | 1/146 (0.7%) | |||
Urticaria | 1/12 (8.3%) | 6/149 (4%) | 3/146 (2.1%) | |||
Vascular disorders | ||||||
Hypertension | 1/12 (8.3%) | 11/149 (7.4%) | 6/146 (4.1%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Communication Center |
---|---|
Organization | Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany |
Phone | +49-6151-72-5200 |
service@emdgroup.com |
- MS200647_0055
- 2019-001992-35