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Bintrafusp Alfa Combination Therapy in Participants With Cervical Cancer (INTR@PID 046)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04551950
Recruitment Status : Completed
First Posted : September 16, 2020
Results First Posted : March 8, 2024
Last Update Posted : March 8, 2024
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cervical Cancer
Interventions Drug: M7824
Drug: Carboplatin
Drug: Paclitaxel
Drug: Bevacizumab
Drug: Cisplatin
Radiation: Radiotherapy
Enrollment 25
Recruitment Details  
Pre-assignment Details A total of 28 participants were screened out of which 25 participants were treated.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Period Title: Overall Study
Started 8 9 8
Treated 8 9 8
Completed 8 9 8
Not Completed 0 0 0
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy Total
Hide Arm/Group Description Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care. Total of all reporting groups
Overall Number of Baseline Participants 8 9 8 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 9 participants 8 participants 25 participants
44  (9) 47  (8.3) 49  (13.1) 47  (10.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 8 participants 25 participants
Female
8
 100.0%
9
 100.0%
8
 100.0%
25
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 8 participants 25 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
  37.5%
3
  33.3%
3
  37.5%
9
  36.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
1
  12.5%
1
   4.0%
White
4
  50.0%
6
  66.7%
3
  37.5%
13
  52.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
  12.5%
0
   0.0%
1
  12.5%
2
   8.0%
Ethnicity  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 8 participants 25 participants
Hispanic or Latino
1
  12.5%
0
   0.0%
0
   0.0%
1
   4.0%
Missing
1
  12.5%
0
   0.0%
0
   0.0%
1
   4.0%
Not Hispanic or Latino
6
  75.0%
9
 100.0%
8
 100.0%
23
  92.0%
1.Primary Outcome
Title Number of Participants With Dose-Limiting Toxicities (DLTs)
Hide Description DLT was defined as Adverse Events (AEs) with any of following toxicities: Grade 4 nonhematologic toxicity or hematologic toxicity lasting more than equal to (>=) 7 days despite medical intervention; Grade 3 nausea, vomiting, and diarrhea lasting >= 3 days despite supportive care; Any Grade 3 or Grade 4 nonhematologic lab value leading to hospitalization or persisting for >= 7 days; Grade 3 or Grade 4: grade 3 is defined as absolute neutrophil count (ANC) less than (<) 1,000/mm3 with a temperature of > 38.3 degree Celsius (°C); grade 4 is defined as ANC < 1,000/mm3 with a temperature of > 38.3°C, with life-threatening consequences; Thrombocytopenia < 25,000/mm3 associated with bleeding not resulting in hemodynamic instability or a life-threatening bleeding resulting in urgent intervention; Bleeding events >= Grade 3 occurring within 5 days of bintrafusp alfa treatment; Prolonged delay (> 3 weeks) in initiating Cycle 2 due to treatment-related toxicity; Grade 5 toxicity.
Time Frame Up to 4 weeks after first administration of study intervention
Hide Outcome Measure Data
Hide Analysis Population Description
Dose-Limiting Toxicity Analysis (DLT) Set included all participants who completed the DLT period (within 4 weeks after first administration of study intervention) with at least 80 Percent (%) of the planned cumulative dose received during this period for each study intervention and/or who experienced at least one DLT during the DLT period.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 8 9 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2
  22.2%
0
   0.0%
2.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide 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. Treatment-Emergent Adverse Events (TEAEs) were defined as events with onset date or worsening during the on-treatment period. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs included serious TEAEs and non-serious TEAEs.
Time Frame Time from first treatment assessed up to approximately 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety (SAF) analysis set included all participants who were administered any dose of any study intervention.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 8 9 8
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
8
 100.0%
9
 100.0%
8
 100.0%
Any Serious TEAEs
7
  87.5%
4
  44.4%
6
  75.0%
3.Secondary Outcome
Title Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa
Hide Description Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Bintrafusp Alfa concentration-time data.
Time Frame Pre-dose Up to 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa
Hide Description Ctrough was the serum concentration observed immediately before next dosing.
Time Frame Pre-dose Up to 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa
Hide Description The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Time Frame Pre-dose Up to 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa
Hide Description AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.
Time Frame Pre-dose Up to 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of Bintrafusp Alfa
Hide Description Cmax was obtained directly from the concentration versus time curve.
Time Frame Pre-dose Up to 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Time to Reach Maximum Serum Concentration (Tmax) of Bintrafusp Alfa
Hide Description The time to reach the maximum observed concentration collected during a dosing interval. Tmax was obtained directly from the concentration versus time curve.
Time Frame Pre-dose Up to 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa
Hide Description Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. Elimination half-life determined as 0.693/ Lamda z(λz), λz=terminal first order (elimination) rate constant.
Time Frame Pre-dose Up to 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Number of Participants With Positive Anti-Drug Antibody (ADA) of Bintrafusp Alfa
Hide Description A validated method was applied to detect ADAs in the presence of drug in human serum. The ADA titers of positive samples were determined.
Time Frame Pre-dose Up to 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
As per changes in planned analysis, the outcome measure related to immunogenicity were not assessed.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Number of Japanese Participants With Dose-Limiting Toxicities (DLTs)
Hide Description DLT was defined as Adverse Events (AEs) with any of following toxicities: Grade 4 nonhematologic toxicity or hematologic toxicity lasting more than equal to (>=) 7 days despite medical intervention; Grade 3 nausea, vomiting, and diarrhea lasting >= 3 days despite supportive care; Any Grade 3 or Grade 4 nonhematologic lab value leading to hospitalization or persisting for >= 7 days; Grade 3 or Grade 4: grade 3 is defined as absolute neutrophil count (ANC) less than (<) 1,000/mm3 with a temperature of > 38.3 degree Celsius (°C); grade 4 is defined as ANC < 1,000/mm3 with a temperature of > 38.3°C, with life-threatening consequences; Thrombocytopenia < 25,000/mm3 associated with bleeding not resulting in hemodynamic instability or a life-threatening bleeding resulting in urgent intervention; Bleeding events >= Grade 3 occurring within 5 days of bintrafusp alfa treatment; Prolonged delay (> 3 weeks) in initiating Cycle 2 due to treatment-related toxicity; Grade 5 toxicity.
Time Frame Up to 4 weeks after first administration of study intervention
Hide Outcome Measure Data
Hide Analysis Population Description
Dose-Limiting Toxicity Analysis (DLT) Set included all participants who completed the DLT period (within 4 weeks after first administration of study intervention) with at least 80 Percent (%) of the planned cumulative dose received during this period for each study intervention and/or who experienced at least one DLT during the DLT period. Number of Participants Analyzed=participants evaluable for this outcome.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 3 3 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2
  66.7%
0
   0.0%
12.Secondary Outcome
Title Number of Japanese Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide 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. Treatment-Emergent Adverse Events (TEAEs) were defined as events with onset date or worsening during the on-treatment period. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important.
Time Frame Time from first treatment assessed up to approximately 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety (SAF) analysis set included all participants who were administered any dose of any study intervention. Number of Participants Analyzed=participants evaluable for this outcome.
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description:
Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
Overall Number of Participants Analyzed 3 3 3
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
3
 100.0%
3
 100.0%
3
 100.0%
Any Serious TEAEs
3
 100.0%
3
 100.0%
3
 100.0%
Time Frame Time from first treatment assessed up to approximately 20 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Hide Arm/Group Description Participants received 2400 miligrams (mg) Bintrafusp alfa along with 50 milligram per square meter (mg/m^2) Cisplatin or Carboplatin, Paclitaxel and 15 milligram per kilogram (mg/kg) Bevacizumab every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Participants received 2400 mg Bintrafusp alfa along with 50 mg/m^2 Cisplatin or Carboplatin, 175 mg/m^2 Paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Participants received 2400 mg Bintrafusp alfa once every 3 weeks along with 40 mg/m^2 Cisplatin weekly for 5 weeks followed by radiotherapy as per standard care.
All-Cause Mortality
Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/8 (25.00%)      2/9 (22.22%)      0/8 (0.00%)    
Hide Serious Adverse Events
Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/8 (87.50%)      4/9 (44.44%)      6/8 (75.00%)    
Blood and lymphatic system disorders       
Anaemia * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Endocrine disorders       
Hyperthyroidism * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Secondary adrenocortical insufficiency * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Gastrointestinal disorders       
Abdominal pain upper * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Colitis * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Lower gastrointestinal haemorrhage * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Rectal haemorrhage * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Small intestinal haemorrhage * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Upper gastrointestinal haemorrhage * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
General disorders       
Pyrexia * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Immune system disorders       
Hypersensitivity * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Infections and infestations       
COVID-19 * 1  1/8 (12.50%)  1/9 (11.11%)  0/8 (0.00%) 
Diverticulitis * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Infection * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Pneumonia * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Urinary tract infection * 1  2/8 (25.00%)  1/9 (11.11%)  1/8 (12.50%) 
Uterine abscess * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Infected neoplasm * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Keratoacanthoma * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Tumour haemorrhage * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Renal and urinary disorders       
Acute kidney injury * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Haematuria * 1  2/8 (25.00%)  0/9 (0.00%)  0/8 (0.00%) 
Reproductive system and breast disorders       
Pelvic pain * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Vaginal haemorrhage * 1  0/8 (0.00%)  2/9 (22.22%)  0/8 (0.00%) 
1
Term from vocabulary, MedDRA 25.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel Cohort 2: Bintrafusp Alfa + Cisplatin+ Radiotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/8 (100.00%)      9/9 (100.00%)      8/8 (100.00%)    
Blood and lymphatic system disorders       
Anaemia * 1  6/8 (75.00%)  7/9 (77.78%)  5/8 (62.50%) 
Febrile neutropenia * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Neutropenia * 1  1/8 (12.50%)  1/9 (11.11%)  1/8 (12.50%) 
Thrombocytopenia * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Cardiac disorders       
Palpitations * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Sinus tachycardia * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Ear and labyrinth disorders       
Tinnitus * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Endocrine disorders       
Hyperthyroidism * 1  2/8 (25.00%)  1/9 (11.11%)  0/8 (0.00%) 
Hypothyroidism * 1  1/8 (12.50%)  1/9 (11.11%)  1/8 (12.50%) 
Secondary adrenocortical insufficiency * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Eye disorders       
Diplopia * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Vision blurred * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Gastrointestinal disorders       
Abdominal pain * 1  4/8 (50.00%)  0/9 (0.00%)  0/8 (0.00%) 
Abdominal pain upper * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Colitis * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Constipation * 1  2/8 (25.00%)  2/9 (22.22%)  3/8 (37.50%) 
Diarrhoea * 1  3/8 (37.50%)  5/9 (55.56%)  8/8 (100.00%) 
Dyspepsia * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Gastritis * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Gastrointestinal angiectasia * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Gingival bleeding * 1  2/8 (25.00%)  3/9 (33.33%)  2/8 (25.00%) 
Lower gastrointestinal haemorrhage * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Melaena * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Mouth haemorrhage * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Nausea * 1  3/8 (37.50%)  6/9 (66.67%)  6/8 (75.00%) 
Periodontal disease * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Proctalgia * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Rectal haemorrhage * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Small intestinal haemorrhage * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Stomatitis * 1  3/8 (37.50%)  3/9 (33.33%)  1/8 (12.50%) 
Upper gastrointestinal haemorrhage * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Vomiting * 1  2/8 (25.00%)  4/9 (44.44%)  4/8 (50.00%) 
General disorders       
Asthenia * 1  3/8 (37.50%)  2/9 (22.22%)  2/8 (25.00%) 
Catheter site pain * 1  0/8 (0.00%)  2/9 (22.22%)  0/8 (0.00%) 
Chest discomfort * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Chills * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Fatigue * 1  2/8 (25.00%)  1/9 (11.11%)  0/8 (0.00%) 
Gait disturbance * 1  0/8 (0.00%)  1/9 (11.11%)  1/8 (12.50%) 
Infusion site extravasation * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Injection site pain * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Malaise * 1  1/8 (12.50%)  1/9 (11.11%)  0/8 (0.00%) 
Oedema peripheral * 1  1/8 (12.50%)  1/9 (11.11%)  0/8 (0.00%) 
Pyrexia * 1  0/8 (0.00%)  2/9 (22.22%)  0/8 (0.00%) 
Hepatobiliary disorders       
Hepatic function abnormal * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Infections and infestations       
COVID-19 * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Coronavirus infection * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Cystitis * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Gingivitis * 1  2/8 (25.00%)  1/9 (11.11%)  0/8 (0.00%) 
Infected dermal cyst * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Infection * 1  1/8 (12.50%)  1/9 (11.11%)  0/8 (0.00%) 
Pelvic abscess * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Skin infection * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Subcutaneous abscess * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Tinea pedis * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Tonsillitis * 1  0/8 (0.00%)  0 1/9 (11.11%)  0/8 (0.00%) 
Urinary tract infection * 1  1/8 (12.50%)  3/9 (33.33%)  1/8 (12.50%) 
Uterine abscess * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Injury, poisoning and procedural complications       
Allergic transfusion reaction * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Animal bite * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Cystitis radiation * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Fall * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Infusion related reaction * 1  0/8 (0.00%)  1/9 (11.11%)  1/8 (12.50%) 
Ligament sprain * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Tooth fracture * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Urinary tract stoma complication * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Wound complication * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Investigations       
Alanine aminotransferase increased * 1  0/8 (0.00%)  3/9 (33.33%)  0/8 (0.00%) 
Amylase increased * 1  1/8 (12.50%)  4/9 (44.44%)  1/8 (12.50%) 
Aspartate aminotransferase increased * 1  0/8 (0.00%)  2/9 (22.22%)  0/8 (0.00%) 
Blood alkaline phosphatase increased * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Blood creatinine increased * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
C-reactive protein increased * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Gamma-glutamyltransferase increased * 1  0/8 (0.00%)  2/9 (22.22%)  0/8 (0.00%) 
Lipase increased * 1  3/8 (37.50%)  2/9 (22.22%)  1/8 (12.50%) 
Lymphocyte count decreased * 1  1/8 (12.50%)  2/9 (22.22%)  1/8 (12.50%) 
Neutrophil count decreased * 1  2/8 (25.00%)  2/9 (22.22%)  2/8 (25.00%) 
Platelet count decreased * 1  2/8 (25.00%)  3/9 (33.33%)  2/8 (25.00%) 
Weight decreased * 1  0/8 (0.00%)  1/9 (11.11%)  2/8 (25.00%) 
White blood cell count decreased * 1  2/8 (25.00%)  2/9 (22.22%)  2/8 (25.00%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  1/8 (12.50%)  1/9 (11.11%)  4/8 (50.00%) 
Dehydration * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Hyperglycaemia * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Hypoalbuminaemia * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Hypocalcaemia * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Hypokalaemia * 1  2/8 (25.00%)  1/9 (11.11%)  0/8 (0.00%) 
Hypomagnesaemia * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Type 2 diabetes mellitus * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  1/8 (12.50%)  4/9 (44.44%)  0/8 (0.00%) 
Back pain * 1  2/8 (25.00%)  1/9 (11.11%)  0/8 (0.00%) 
Muscle spasms * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Muscular weakness * 1  0/8 (0.00%)  1/9 (11.11%)  1/8 (12.50%) 
Musculoskeletal pain * 1  2/8 (25.00%)  3/9 (33.33%)  0/8 (0.00%) 
Myalgia * 1  1/8 (12.50%)  2/9 (22.22%)  0/8 (0.00%) 
Pain in extremity * 1  2/8 (25.00%)  2/9 (22.22%)  1/8 (12.50%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer pain * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Infected neoplasm * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Keratoacanthoma * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Melanocytic naevus * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Squamous cell carcinoma * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Tumour haemorrhage * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Tumour necrosis * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Nervous system disorders       
Dizziness * 1  0/8 (0.00%)  2/9 (22.22%)  1/8 (12.50%) 
Dysaesthesia * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Dysgeusia * 1  2/8 (25.00%)  1/9 (11.11%)  3/8 (37.50%) 
Facial paralysis * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Headache * 1  2/8 (25.00%)  3/9 (33.33%)  3/8 (37.50%) 
Hypoaesthesia * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Neuropathy peripheral * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Neurotoxicity * 1  2/8 (25.00%)  4/9 (44.44%)  0/8 (0.00%) 
Paraesthesia * 1  0/8 (0.00%)  1/9 (11.11%)  1/8 (12.50%) 
Peripheral sensory neuropathy * 1  3/8 (37.50%)  2/9 (22.22%)  0/8 (0.00%) 
Presyncope * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Radiculopathy * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Product Issues       
Thrombosis in device * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Psychiatric disorders       
Adjustment disorder * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Anxiety * 1  0/8 (0.00%)  0/9 (0.00%)  2/8 (25.00%) 
Insomnia * 1  1/8 (12.50%)  2/9 (22.22%)  1/8 (12.50%) 
Mania * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Mood swings * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Renal and urinary disorders       
Diabetic nephropathy * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Dysuria * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Haematuria * 1  2/8 (25.00%)  0/9 (0.00%)  0/8 (0.00%) 
Proteinuria * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Reproductive system and breast disorders       
Breast pain * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Heavy menstrual bleeding * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Intermenstrual bleeding * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Pelvic pain * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Vaginal discharge * 1  1/8 (12.50%)  0/9 (0.00%)  2/8 (25.00%) 
Vaginal haemorrhage * 1  1/8 (12.50%)  3/9 (33.33%)  2/8 (25.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Dyspnoea * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Epistaxis * 1  4/8 (50.00%)  2/9 (22.22%)  0/8 (0.00%) 
Nasal congestion * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Oropharyngeal pain * 1  1/8 (12.50%)  2/9 (22.22%)  1/8 (12.50%) 
Pulmonary embolism * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Rhinitis allergic * 1  1/8 (12.50%)  0/9 (0.00%)  1/8 (12.50%) 
Skin and subcutaneous tissue disorders       
Acne * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Alopecia * 1  3/8 (37.50%)  5/9 (55.56%)  0/8 (0.00%) 
Asteatosis * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Dermatitis acneiform * 1  3/8 (37.50%)  0/9 (0.00%)  2/8 (25.00%) 
Dermatitis allergic * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Dermatitis contact * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Drug eruption * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Dry skin * 1  1/8 (12.50%)  2/9 (22.22%)  2/8 (25.00%) 
Eczema * 1  0/8 (0.00%)  1/9 (11.11%)  1/8 (12.50%) 
Nail discolouration * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Prurigo * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Pruritus * 1  2/8 (25.00%)  3/9 (33.33%)  4/8 (50.00%) 
Purpura * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Rash * 1  0/8 (0.00%)  3/9 (33.33%)  2/8 (25.00%) 
Rash maculo-papular * 1  1/8 (12.50%)  3/9 (33.33%)  3/8 (37.50%) 
Rash papular * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Rash pruritic * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Skin hyperpigmentation * 1  0/8 (0.00%)  2/9 (22.22%)  0/8 (0.00%) 
Skin mass * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Skin texture abnormal * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Skin toxicity * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Urticaria * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Social circumstances       
Menopause * 1  0/8 (0.00%)  0/9 (0.00%)  1/8 (12.50%) 
Vascular disorders       
Arteriosclerosis * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Embolism * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Flushing * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
Hot flush * 1  0/8 (0.00%)  1/9 (11.11%)  1/8 (12.50%) 
Hypertension * 1  1/8 (12.50%)  0/9 (0.00%)  0/8 (0.00%) 
Hypotension * 1  1/8 (12.50%)  1/9 (11.11%)  0/8 (0.00%) 
Lymphoedema * 1  0/8 (0.00%)  1/9 (11.11%)  1/8 (12.50%) 
Phlebitis * 1  0/8 (0.00%)  1/9 (11.11%)  0/8 (0.00%) 
1
Term from vocabulary, MedDRA 25.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
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
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Name/Title: Communication Center
Organization: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
EMail: service@emdgroup.com
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Responsible Party: EMD Serono ( EMD Serono Research & Development Institute, Inc. )
ClinicalTrials.gov Identifier: NCT04551950    
Other Study ID Numbers: MS200647_0046
2020-001561-36 ( EudraCT Number )
First Submitted: September 7, 2020
First Posted: September 16, 2020
Results First Submitted: July 31, 2023
Results First Posted: March 8, 2024
Last Update Posted: March 8, 2024