Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Of Avelumab In Patients With Locally Advanced Or Metastatic Urothelial Cancer (JAVELIN Bladder 100)

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: NCT02603432
Recruitment Status : Active, not recruiting
First Posted : November 11, 2015
Results First Posted : December 17, 2020
Last Update Posted : February 8, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Urothelial Cancer
Interventions Biological: Avelumab
Other: Best Supportive Care
Biological: Following the planned interim analysis for this study: Avelumab
Enrollment 700
Recruitment Details This study included only those participants who did not show evidence of disease progression after completion of at least 4 and not more than 6 cycles of first-line platinum-containing chemotherapy (prior to this study).
Pre-assignment Details  
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy. As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Period Title: Overall Study
Started 350 350
Completed 0 0
Not Completed 350 350
Reason Not Completed
Ongoing             184             144
Adverse Event             1             0
Death             144             177
Lost to Follow-up             4             6
Progressive Disease             5             5
Withdrawal by Subject             9             17
No Longer Meets Eligibility Criteria             3             0
Other             0             1
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care Total
Hide Arm/Group Description Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy. As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy. Total of all reporting groups
Overall Number of Baseline Participants 350 350 700
Hide Baseline Analysis Population Description
The full analysis set included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 350 participants 350 participants 700 participants
67.20  (9.52) 67.7  (9.20) 67.44  (9.40)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 350 participants 350 participants 700 participants
Female
84
  24.0%
75
  21.4%
159
  22.7%
Male
266
  76.0%
275
  78.6%
541
  77.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 350 participants 350 participants 700 participants
Hispanic or Latino
18
   5.1%
12
   3.4%
30
   4.3%
Not Hispanic or Latino
286
  81.7%
298
  85.1%
584
  83.4%
Unknown or Not Reported
46
  13.1%
40
  11.4%
86
  12.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 350 participants 350 participants 700 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
75
  21.4%
81
  23.1%
156
  22.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   0.6%
0
   0.0%
2
   0.3%
White
232
  66.3%
238
  68.0%
470
  67.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
41
  11.7%
31
   8.9%
72
  10.3%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
Time Frame From randomization to discontinuation from the study, death or date of censoring, whichever occurred first (maximum duration of up to 41 months at the time of final analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 350 350
Median (95% Confidence Interval)
Unit of Measure: months
21.4
(18.9 to 26.1)
14.3
(12.9 to 17.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Avelumab + Best Supportive Care (BSC), Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments One-sided log-rank test was used.
Method Log Rank
Comments Analysis was performed using a Cox's Proportional Hazard model.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.556 to 0.863
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
Hide Description BICR assessed PFS: Duration from randomization until disease progression (PD) or death. PD as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was defined for target disease as at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute increase of at least 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Appearance of any new unequivocal malignant lesion was also considered PD. Analysis was performed using Kaplan-Meier. PFS data was censored on date of last adequate tumor assessment for participants with no event (PD or death), who started new anti-cancer therapy prior to an event or with an event after 2 or more missing tumor assessments.
Time Frame From randomization to date of progression of disease, discontinuation from the study, death or date of censoring, whichever occurred first (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 350 350
Median (95% Confidence Interval)
Unit of Measure: months
3.7
(3.5 to 5.5)
2.0
(1.9 to 2.7)
3.Secondary Outcome
Title Progression-Free Survival (PFS) as Assessed by Investigator
Hide Description Investigator assessed PFS: Duration from randomization to first documentation of PD or death, whichever occurred first. PD as per RECIST version 1.1 was defined for target disease as at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute increase of at least 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Appearance of any new unequivocal malignant lesion was also considered PD. Analysis was performed using Kaplan-Meier. PFS data was censored on date of last adequate tumor assessment for participants with no event (PD or death), who started a new anti-cancer therapy prior to an event or with an event after 2 or more missing tumor assessments.
Time Frame From randomization to date of progression of disease, discontinuation from the study, death or date of censoring, whichever occurred first (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 350 350
Median (95% Confidence Interval)
Unit of Measure: months
5.5
(4.2 to 7.2)
2.1
(1.9 to 3.0)
4.Secondary Outcome
Title Percentage of Participants With Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR)
Hide Description BICR assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
Time Frame From randomization to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 350 350
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
9.7
(6.8 to 13.3)
1.4
(0.5 to 3.3)
5.Secondary Outcome
Title Percentage of Participants With Objective Response as Assessed by Investigator
Hide Description Investigator assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of CR or PR. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. A CR also required normalization of tumor marker levels and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
Time Frame From randomization to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 350 350
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.3
(9.0 to 16.2)
3.4
(1.8 to 5.9)
6.Secondary Outcome
Title Time to Tumor Response (TTR) as Assessed by Blinded Independent Central Review (BICR)
Hide Description TTR was defined, for participants with an objective response as the time from 'start date' to the first documentation of objective tumor response (CR or PR), which was confirmed subsequently. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
Time Frame From the date of randomization to the first documentation of objective response (CR or PR) (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants. Here, 'Overall Number of participants analyzed (N)' signifies participants who were evaluable for this outcome measure (OM).
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 34 5
Median (Full Range)
Unit of Measure: months
2.0
(1.7 to 16.4)
2.0
(1.8 to 7.0)
7.Secondary Outcome
Title Time to Tumor Response (TTR) as Assessed by Investigator
Hide Description TTR was defined, for participants with an objective response as the time from 'start date' to the first documentation of objective tumor response (CR or PR). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. A CR also required normalization of tumor marker levels and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
Time Frame From the date of randomization to the first documentation of objective response (CR or PR) (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants. Here, 'Overall Number of participants analyzed' signifies participants who were evaluable for this outcome measure.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 43 12
Median (Full Range)
Unit of Measure: months
2.0
(1.8 to 22.2)
1.9
(1.1 to 10.9)
8.Secondary Outcome
Title Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR)
Hide Description BICR assessed DOR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR: complete disappearance of all target and non-target lesions, with exception of nodal disease sustained for 4 weeks. Any pathological lymph nodes reduced in short axis to <10 mm. PR: at least 30% decrease in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions. PD for target disease: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study and relative increase of 20%, sum also demonstrated absolute increase of at least 5 mm. PD for non-target disease: unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Appearance of any new unequivocal malignant lesion was also considered PD.
Time Frame First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on subset of randomized participants, who had objective response, as assessed by BICR.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 34 5
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(15.6 to NA)
NA [2] 
(NA to NA)
[1]
Median and upper limit of 95% Confidence Interval (CI) were not estimable due to limited number of events.
[2]
Median and 95% CI were not estimable due to limited number of events.
9.Secondary Outcome
Title Duration of Response (DOR) as Assessed by Investigator
Hide Description Investigator assessed DOR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR: complete disappearance of all target and non-target lesions, with exception of nodal disease sustained for 4 weeks. Additionally, normalization of tumor marker levels and any pathological lymph nodes reduced in short axis to <10 mm. PR: at least 30% decrease in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions. PD for target disease: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study and relative increase of 20%, sum also demonstrated absolute increase of at least 5 mm. PD for non-target disease: unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Appearance of any new unequivocal malignant lesion was also considered PD.
Time Frame First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on subset of randomized participants, who had objective response, as assessed by Investigator.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 43 12
Median (95% Confidence Interval)
Unit of Measure: months
25.6 [1] 
(12.0 to NA)
NA [2] 
(3.6 to NA)
[1]
The upper limit of 95% CI was not estimable due to limited number of events.
[2]
Median and upper limit of 95% CI were not estimable due to limited number of events.
10.Secondary Outcome
Title Percentage of Participants With Disease Control (DC) as Assessed by Blinded Independent Central Review (BICR)
Hide Description Disease Control (DC) was defined as a best overall response of CR, PR, non-CR/non-PD or stable disease (SD) as assessed by BICR. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Non-CR/Non-PD was defined as persistence of any non-target lesions and/or tumor marker level above the normal limits. SD was defined as not to qualify for CR, PR or PD for target lesions and followed PR only if the sum increased by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds.
Time Frame From randomization to PD, death or start of new anti-cancer therapy (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 350 350
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.1
(35.9 to 46.5)
27.4
(22.8 to 32.4)
11.Secondary Outcome
Title Percentage of Participants With Disease Control (DC) as Assessed by Investigator
Hide Description DC was defined as a best overall response of CR, PR, non-CR/non-PD or SD as assessed by Investigator. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Additionally, normalization of tumor marker levels and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Non-CR/Non-PD was defined as persistence of any non-target lesions and/or tumor marker level above the normal limits. SD was defined as not to qualify for CR, PR or PD for target lesions and followed PR only if the sum increased by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds.
Time Frame From randomization to PD, death or start of new anti-cancer therapy (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 350 350
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50.9
(45.5 to 56.2)
34.0
(29.0 to 39.2)
12.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on, National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent AEs are events between first dose of study drug and up to 90 days after last dose of study drug or end of treatment (EOT) visit, that were absent before treatment or that worsened relative to pretreatment state.
Time Frame For "Avelumab + Best Supportive Care (BSC)'' group: Day 1 up to 90 days after last dose of study drug; for "Best Supportive Care'' group: Day 1 up to 90 days after EOT visit, for a maximum duration of up to 41 months at the time of the analysis
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who had received at least one dose of study drug on arm 'Avelumab+BSC' or completed C1D1 on arm 'BSC'. Here "Overall number of participants analyzed" signifies participants with at least one treatment-emergent AE of Grade 1, Grade 2, Grade 3, Grade 4 or Grade 5.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 337 267
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 1
51
  15.1%
77
  28.8%
Grade 2
123
  36.5%
103
  38.6%
Grade 3
147
  43.6%
56
  21.0%
Grade 4
12
   3.6%
7
   2.6%
Grade 5
4
   1.2%
24
   9.0%
13.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities Greater Than or Equal to (>=) Grade 3 (G3), Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Hide Description Hematology (Anemia G3: hemoglobin<8.0 grams per deciliter [g/dL],<4.9 mmol/L,<80 g/L, transfusion indicated, Grade 4 [G4]: life-threatening consequences, urgent intervention indicated, Grade 5 [G5]: death; platelet count decreased-G3:<50.0 to 25.0*10^9/L, G4: <25.0*10^9/L; lymphocyte count decreased-G3:<0.5-0.2*10^9/L, G4:<0.2*10^9/L; neutrophil count decreased-G3:<1.0 to 0.5*10^9 /L, G4:<0.5*10^9/L). Chemistry (creatinine increased-G3:>3.0 to 6.0*upper limit of normal [ULN], G4:>6.0*ULN; serum amylase increased, lipase increased-G3:>2.0- 5.0*ULN, G4:>5.0*ULN. Aspartate aminotransferase [AST], alanine aminotransferase [ALT]-G3:>5.0 to 20.0*ULN, G4:>20.0*ULN]. Blood bilirubin increased-[G3:>3.0 to 10.0*ULN, G4:>10.0*ULN], Creatine phosphokinase [CPK] increased- [G3:>5.0 to 10.0*ULN, G4:>10.0*ULN], Hyperglycemia-[G3:>250 to 500 mg/dL; >13.9 to 27.8 mmol/L hospitalization indicated, G4:>500 mg/DL; >27.8 mmol/L life-threatening consequences]).
Time Frame For "Avelumab + Best Supportive Care (BSC)'' group: Day 1 up to 90 days after last dose of study drug; for "Best Supportive Care'' group: Day 1 up to 90 days after EOT visit, for a maximum duration of up to 41 months at the time of the analysis
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who had received at least one dose of study drug on arm 'Avelumab+BSC' or completed C1D1 on arm 'BSC'. Here, 'Number analyzed (n)' = Participants evaluable for this outcome measure for each specified rows.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 344 345
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia Number Analyzed 344 participants 339 participants
15
   4.4%
12
   3.5%
Platelet Count Decreased Number Analyzed 344 participants 339 participants
2
   0.6%
1
   0.3%
Lymphocyte Count Decreased Number Analyzed 344 participants 339 participants
18
   5.2%
11
   3.2%
Neutrophil Count Decreased Number Analyzed 344 participants 339 participants
6
   1.7%
0
   0.0%
Creatinine Increased Number Analyzed 344 participants 341 participants
5
   1.5%
4
   1.2%
Serum Amylase Increased Number Analyzed 339 participants 329 participants
20
   5.9%
9
   2.7%
Lipase Increased Number Analyzed 343 participants 333 participants
29
   8.5%
22
   6.6%
ALT Increased Number Analyzed 344 participants 341 participants
9
   2.6%
2
   0.6%
AST Increased Number Analyzed 344 participants 340 participants
6
   1.7%
3
   0.9%
Blood Bilirubin Increased Number Analyzed 344 participants 341 participants
0
   0.0%
3
   0.9%
CPK Increased Number Analyzed 339 participants 332 participants
8
   2.4%
0
   0.0%
Hyperglycemia Number Analyzed 344 participants 341 participants
27
   7.8%
18
   5.3%
14.Secondary Outcome
Title Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit
Hide Description Vital signs included blood pressure and pulse rate. Blood pressure included sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP).
Time Frame Baseline (D1 of Cycle 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7, EOT visit (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set analyzed. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified time points.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 344 345
Mean (Standard Deviation)
Unit of Measure: millimeters of mercury
Baseline (C1D1): Sitting DBP Number Analyzed 324 participants 329 participants
75.7  (10.81) 77.0  (10.48)
Change at Cycle 2, Day 1: Sitting DBP Number Analyzed 295 participants 287 participants
-0.9  (9.37) -0.0  (9.06)
Change at Cycle 3, Day 1: Sitting DBP Number Analyzed 268 participants 228 participants
-1.7  (10.36) -1.6  (9.38)
Change at Cycle 4, Day 1: Sitting DBP Number Analyzed 230 participants 153 participants
-1.7  (9.97) -1.0  (9.90)
Change at Cycle 5, Day 1: Sitting DBP Number Analyzed 201 participants 119 participants
-1.1  (10.60) -1.0  (10.22)
Change at Cycle 6, Day 1: Sitting DBP Number Analyzed 181 participants 107 participants
-1.2  (10.89) -1.1  (10.89)
Change at Cycle 7, Day 1: Sitting DBP Number Analyzed 158 participants 81 participants
-0.7  (10.90) 0.2  (9.95)
Change at End of Treatment: Sitting DBP Number Analyzed 190 participants 237 participants
-0.1  (12.09) -1.7  (10.23)
Baseline (C1D1): Sitting SBP Number Analyzed 324 participants 329 participants
131.3  (17.34) 130.6  (16.32)
Change at Cycle 2, Day 1: Sitting SBP Number Analyzed 295 participants 287 participants
-2.2  (14.85) -0.3  (13.79)
Change at Cycle 3, Day 1: Sitting SBP Number Analyzed 268 participants 228 participants
-1.9  (16.10) 1.0  (14.94)
Change at Cycle 4, Day 1: Sitting SBP Number Analyzed 230 participants 153 participants
-0.6  (16.54) 1.3  (16.54)
Change at Cycle 5, Day 1: Sitting SBP Number Analyzed 201 participants 119 participants
-1.9  (15.49) 1.9  (15.85)
Change at Cycle 6, Day 1: Sitting SBP Number Analyzed 181 participants 107 participants
-2.3  (15.77) 3.3  (16.81)
Change at Cycle 7, Day 1: Sitting SBP Number Analyzed 158 participants 81 participants
-1.8  (16.13) 2.7  (19.86)
Change at End of Treatment: Sitting SBP Number Analyzed 190 participants 237 participants
-0.9  (18.99) -0.3  (16.78)
15.Secondary Outcome
Title Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit
Hide Description Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized.
Time Frame Baseline (D1 of Cycle 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7, EOT visit (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set analyzed. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified time points.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 344 345
Mean (Standard Deviation)
Unit of Measure: beats per minute
Baseline (C1D1) Number Analyzed 324 participants 327 participants
76.1  (12.84) 77.1  (12.95)
Change at Cycle 2, Day 1 Number Analyzed 295 participants 286 participants
0.3  (11.81) 0.1  (9.98)
Change at Cycle 3, Day 1 Number Analyzed 268 participants 226 participants
-0.2  (12.10) -0.4  (10.20)
Change at Cycle 4, Day 1 Number Analyzed 230 participants 152 participants
-0.5  (12.84) -0.1  (11.26)
Change at Cycle 5, Day 1 Number Analyzed 201 participants 118 participants
0.4  (12.32) -1.0  (11.45)
Change at Cycle 6, Day 1 Number Analyzed 181 participants 105 participants
-0.8  (11.54) -2.6  (10.52)
Change at Cycle 7, Day 1 Number Analyzed 158 participants 80 participants
-0.6  (11.89) -2.6  (11.48)
Change at End of Treatment Number Analyzed 190 participants 235 participants
2.5  (12.25) 1.4  (12.45)
16.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Avelumab
Hide Description The LLQ of avelumab was 0.20 mcg/mL. Data for this outcome measure was not collected for reporting group "Best Supportive Care", since avelumab was not administered in this arm.
Time Frame End of avelumab infusion on Day 1 of Cycle 1, 2, 3, 5, 7, 9, 11, 13 and Day 15 of Cycle 1, 2, 3
Hide Outcome Measure Data
Hide Analysis Population Description
Avelumab pharmacokinetic (PK) parameter analysis set: all participants who received at least one dose of avelumab and who had at least one post-dose concentration measurement above the LLQ for avelumab. Here, 'n' signifies participants evaluable for this OM at specified time points.
Arm/Group Title Avelumab + Best Supportive Care (BSC)
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 344
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram per milliliter (mcg/mL)
Cycle 1, Day 1 Number Analyzed 295 participants
192.7
(68.4%)
Cycle 1, Day 15 Number Analyzed 283 participants
216.2
(49.6%)
Cycle 2, Day 1 Number Analyzed 274 participants
201.5
(54.5%)
Cycle 2, Day 15 Number Analyzed 262 participants
208.5
(60.2%)
Cycle 3, Day 1 Number Analyzed 251 participants
213.1
(39.6%)
Cycle 3, Day 15 Number Analyzed 228 participants
213.1
(52.7%)
Cycle 5, Day 1 Number Analyzed 179 participants
197.5
(67.7%)
Cycle 7, Day 1 Number Analyzed 147 participants
191.9
(86.2%)
Cycle 9, Day 1 Number Analyzed 111 participants
168.9
(84.4%)
Cycle 11, Day 1 Number Analyzed 86 participants
203.4
(51.6%)
Cycle 13, Day 1 Number Analyzed 74 participants
222.8
(30.3%)
17.Secondary Outcome
Title Predose Plasma Concentration (Ctrough) of Avelumab
Hide Description The LLQ of avelumab was 0.20 mcg/mL. Data for this outcome measure was not collected for reporting group "Best Supportive Care", since avelumab was not administered in this arm.
Time Frame Pre-dose (0 hour) on Day 1 of Cycle 1, 2, 3, 5, 7, 9, 11, 13 and Day 15 of Cycle 1, 2, 3
Hide Outcome Measure Data
Hide Analysis Population Description
Avelumab PK parameter analysis set: all participants who received at least one dose of avelumab and who had at least one post-dose concentration measurement above the LLQ for avelumab. Here, 'n' signifies participants evaluable for this OM at specified time points.
Arm/Group Title Avelumab + Best Supportive Care (BSC)
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 344
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram per milliliter (mcg/mL)
Cycle 1, Day 1 Number Analyzed 321 participants
3.1
(247.6%)
Cycle 1, Day 15 Number Analyzed 296 participants
22.2
(48.6%)
Cycle 2, Day 1 Number Analyzed 268 participants
25.2
(64.2%)
Cycle 2, Day 15 Number Analyzed 253 participants
26.5
(65.4%)
Cycle 3, Day 1 Number Analyzed 240 participants
26.4
(76.2%)
Cycle 3, Day 15 Number Analyzed 220 participants
25.7
(85.2%)
Cycle 5, Day 1 Number Analyzed 183 participants
26.8
(67.5%)
Cycle 7, Day 1 Number Analyzed 146 participants
29.7
(60.2%)
Cycle 9, Day 1 Number Analyzed 111 participants
32.4
(55.9%)
Cycle 11, Day 1 Number Analyzed 90 participants
29.8
(68.9%)
Cycle 13, Day 1 Number Analyzed 75 participants
32.4
(54.9%)
18.Secondary Outcome
Title Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
Hide Description ADA against avelumab in serum samples was determined and reported separately for ADA never positive and ADA ever positive participants. Participants were considered ADA ever-positive if they had at least one positive ADA result at any time point during study and were otherwise considered negative. Data for this outcome measure was not planned to be collected and analyzed for reporting arm "Best Supportive Care", since, avelumab was not administered in this arm.
Time Frame From randomization up to the 30-Day Follow-up visit (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis set included all participants who had received at least one dose of study drug and who had at least one ADA sample collected for avelumab in the avelumab containing arm.
Arm/Group Title Avelumab + Best Supportive Care (BSC)
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 344
Measure Type: Count of Participants
Unit of Measure: Participants
Never-positive
278
  80.8%
Ever-positve
66
  19.2%
19.Secondary Outcome
Title Number of ADA Ever Positive Participants For Each Serum of ADA Titers for Avelumab
Hide Description Serum samples were assayed for ADA using a validated analytical method. Number of ADA ever positive participants for each serum of ADA titer (60, 180, 540, 1620, 4860, 14580, and 43740) are reported.
Time Frame From randomization up to the 30-Day Follow-up visit (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on participants who had received at least one dose of study drug and who had ADA ever-positive results. Here "Overall number of participants analyzed" signifies participants who had data available for this outcome measure.
Arm/Group Title Avelumab + Best Supportive Care (BSC)
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 66
Measure Type: Count of Participants
Unit of Measure: Participants
60
4
   6.1%
180
14
  21.2%
540
18
  27.3%
1620
11
  16.7%
4860
11
  16.7%
14580
7
  10.6%
43740
1
   1.5%
20.Secondary Outcome
Title Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never Positive and Ever Positive Status
Hide Description [Not Specified]
Time Frame Up to approximately 60 months
Outcome Measure Data Not Reported
21.Secondary Outcome
Title Number of Participants With Programmed Death Receptor-1 Ligand 1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)
Hide Description PD-L1 assessment was performed using immunohistochemistry on pre-treatment tumor tissue samples. Participants were classified as having PD-L1 -positive status if at least one of the following three criteria were met: at least 25% of tumor cells stained for PD-L1, at least 25% of immune cells stained for PD-L1 if more than 1% of the tumor area contained immune cells, or 100% of immune cells stained for PD-L1 if no more than 1% of the tumor area contained immune cells.
Time Frame Up to 41 months at the time of the analysis
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 350 350
Measure Type: Count of Participants
Unit of Measure: Participants
Positive
189
  54.0%
169
  48.3%
Negative
139
  39.7%
131
  37.4%
Unknown
22
   6.3%
50
  14.3%
22.Secondary Outcome
Title Number of Participants With Cluster of Differentiation 8 (CD8) T Lymphocytes (Cytotoxic T Lymphocytes)
Hide Description [Not Specified]
Time Frame Up to approximately 60 months
Outcome Measure Data Not Reported
23.Secondary Outcome
Title Change From Baseline in National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Score at Day 1 of Cycle 6
Hide Description NCCN-FACT FBlSI-18 is an 18-item participant completed questionnaire, designed to assess impact of cancer therapy on urothelial cancer-related symptoms and quality of life based on numerical point scoring of symptoms/concerns. It included four subscales: Disease related symptoms- physical subscale with 9 items, disease related symptoms- emotional subscale with 2 items, treatment side effects subscale with 5 items and general function/well-being subscale with 2 items. Participants rated their level of symptoms for each item using 5-point scale ranging from 0=not at all to 4=very much. Items that were negatively framed, and the scores were reversed for analysis so that higher scores= good quality of life. Overall score: total of 18 items, ranging from 0=severely symptomatic to 72=asymptomatic. Higher scores= better functioning or lower symptom burden.
Time Frame Baseline, Day 1 of Cycle 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants who had data available for this outcome measure and 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 332 329
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 332 participants 329 participants
53.3  (9.59) 52.7  (9.31)
Change at Day 1 of Cycle 6 Number Analyzed 178 participants 109 participants
1.0  (8.25) 1.6  (8.35)
24.Secondary Outcome
Title Time to Deterioration (TTD) Based on National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Disease Related Symptoms-Physical Subscale (DRS-P) Scores
Hide Description NCCN-FACT FBlSI-18: an 18-item participant completed questionnaire, designed to assess impact of cancer therapy on urothelial cancer-related symptoms and quality of life based on numerical point scoring of symptoms/concerns. It included four subscales: Disease related symptoms-physical subscale with 9 items,disease related symptoms-emotional subscale with 2 items, treatment side effects subscale with 5 items,general function/well-being subscale with 2 items. Participants rated their level of symptoms for each item using 5-point scale ranging: 0=not at all to 4=very much. For items negatively framed, scores were reversed for analysis so that higher scores= good quality of life. DRS-P score: total 9 items, ranging from 0=severely symptomatic to 36= asymptomatic. Higher scores=better functioning or lower symptom burden. TTD: time from randomization to first time participant's score showed 3 point or greater decrease from baseline in FBlSI-DRS-P subscale for 2 consecutive assessments.
Time Frame From randomization up to the 90-Day Follow-up Visit (maximum duration of up to 41 months at the time of the analysis)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all randomized participants.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 350 350
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(13.9 to NA)
13.8 [2] 
(12.9 to NA)
[1]
Median and upper limit of 95% CI were not estimable due to the small number of events.
[2]
The upper limit of 95% CI was not estimable due to the small number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Avelumab + Best Supportive Care (BSC), Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9130
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.26
Confidence Interval (1-Sided) 95%
0.901
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Utility Score at Cycle 6
Hide Description The EQ-5D-5L was a 6-item participant-completed questionnaire designed to assess health status in terms of a single utility score. There were 2 components to the EQ-5D-5L, a Health State Profile which had individuals rate their level of problems (none, slight, moderate, severe, extreme/unable) in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and a Visual Analogue Scale (VAS) in which participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable). Published UK weights was used to create a single summary utility score. Utility scores range from -0.594 to 1, with low scores representing lower health status.
Time Frame Baseline, Day 1 of Cycle 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all participants who were randomized. Here, 'Overall number of participants analyzed' signifies participants who had data available for this outcome measure and 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 336 327
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 336 participants 327 participants
0.814  (0.1794) 0.792  (0.2013)
Change at Day 1 of Cycle 6 Number Analyzed 181 participants 111 participants
-0.029  (0.1919) -0.020  (0.1684)
26.Secondary Outcome
Title Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) - Visual Analog Scale (VAS) Score at Cycle 6
Hide Description The EQ-5D-5L was a 6-item participant-completed questionnaire designed to assess health status in terms of a single utility score. There were 2 components to the EQ-5D-5L, a Health State Profile which had individuals rate their level of problems (none, slight, moderate, severe, extreme/unable) in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and a Visual Analogue Scale (VAS) in which participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
Time Frame Baseline, Day 1 of Cycle 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all participants who were randomized. Here, 'Overall number of participants analyzed' signifies participants who had data available for this outcome measure and 'number analyzed' signifies participants evaluable for this outcome measure at specified time points.
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description:
Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
Overall Number of Participants Analyzed 335 325
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 335 participants 325 participants
74.9  (18.87) 74.9  (16.34)
Change at Day 1 of Cycle 6 Number Analyzed 183 participants 109 participants
1.6  (17.74) 0.2  (14.74)
Time Frame For ''Avelumab + Best Supportive Care (BSC)'' reporting group: Day 1 up to 90 days after last dose of study drug and for ''Best Supportive Care'' reporting group: Day 1 up to 90 days after end of treatment visit, for a maximum duration of up to 41 months at the time of the analysis
Adverse Event Reporting Description Same event may appear as both an AE and Serious Adverse Events (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. All-Cause Mortality was assessed in the full analysis set. Serious and Other (Not including Serious) Adverse Events were monitored/assessed in the Safety Analysis set.
 
Arm/Group Title Avelumab + Best Supportive Care (BSC) Best Supportive Care
Hide Arm/Group Description Participants received an intravenous (IV) infusion of 10 milligrams per kilograms (mg/kg) of Avelumab along with BSC, on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. BSC was administered as per the treating physician. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy. As prescribed by the treating physician, participants received BSC which included treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first. Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anti-cancer therapy.
All-Cause Mortality
Avelumab + Best Supportive Care (BSC) Best Supportive Care
Affected / at Risk (%) Affected / at Risk (%)
Total   144/344 (41.86%)   177/345 (51.30%) 
Hide Serious Adverse Events
Avelumab + Best Supportive Care (BSC) Best Supportive Care
Affected / at Risk (%) Affected / at Risk (%)
Total   96/344 (27.91%)   69/345 (20.00%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/344 (0.29%)  2/345 (0.58%) 
Cardiac disorders     
Acute myocardial infarction * 1  1/344 (0.29%)  0/345 (0.00%) 
Atrial fibrillation * 1  3/344 (0.87%)  1/345 (0.29%) 
Cardiogenic shock * 1  0/344 (0.00%)  1/345 (0.29%) 
Coronary artery disease * 1  1/344 (0.29%)  0/345 (0.00%) 
Coronary artery stenosis * 1  1/344 (0.29%)  0/345 (0.00%) 
Myocardial infarction * 1  2/344 (0.58%)  0/345 (0.00%) 
Sinus tachycardia * 1  1/344 (0.29%)  0/345 (0.00%) 
Supraventricular tachycardia * 1  1/344 (0.29%)  0/345 (0.00%) 
Ear and labyrinth disorders     
Vertigo positional * 1  1/344 (0.29%)  0/345 (0.00%) 
Endocrine disorders     
Hyperthyroidism * 1  1/344 (0.29%)  0/345 (0.00%) 
Hypothyroidism * 1  1/344 (0.29%)  0/345 (0.00%) 
Eye disorders     
Erythema of eyelid * 1  0/344 (0.00%)  1/345 (0.29%) 
Eyelid pain * 1  0/344 (0.00%)  1/345 (0.29%) 
Swelling of eyelid * 1  0/344 (0.00%)  1/345 (0.29%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/344 (0.29%)  3/345 (0.87%) 
Autoimmune pancreatitis * 1  1/344 (0.29%)  0/345 (0.00%) 
Colitis * 1  2/344 (0.58%)  0/345 (0.00%) 
Constipation * 1  2/344 (0.58%)  0/345 (0.00%) 
Diarrhoea * 1  0/344 (0.00%)  1/345 (0.29%) 
Enteritis * 1  1/344 (0.29%)  0/345 (0.00%) 
Gastric ulcer * 1  1/344 (0.29%)  0/345 (0.00%) 
Gastric ulcer haemorrhage * 1  1/344 (0.29%)  0/345 (0.00%) 
Ileus * 1  3/344 (0.87%)  1/345 (0.29%) 
Pancreatitis acute * 1  1/344 (0.29%)  0/345 (0.00%) 
Pancreatitis chronic * 1  0/344 (0.00%)  1/345 (0.29%) 
Vomiting * 1  3/344 (0.87%)  0/345 (0.00%) 
General disorders     
Chest pain * 1  0/344 (0.00%)  1/345 (0.29%) 
Disease progression * 1  3/344 (0.87%)  16/345 (4.64%) 
Fatigue * 1  0/344 (0.00%)  1/345 (0.29%) 
General physical health deterioration * 1  1/344 (0.29%)  1/345 (0.29%) 
Incarcerated hernia * 1  0/344 (0.00%)  1/345 (0.29%) 
Malaise * 1  1/344 (0.29%)  1/345 (0.29%) 
Mass * 1  0/344 (0.00%)  1/345 (0.29%) 
Pain * 1  4/344 (1.16%)  1/345 (0.29%) 
Pyrexia * 1  2/344 (0.58%)  1/345 (0.29%) 
Systemic inflammatory response syndrome * 1  1/344 (0.29%)  0/345 (0.00%) 
Thirst * 1  1/344 (0.29%)  0/345 (0.00%) 
Hepatobiliary disorders     
Autoimmune hepatitis * 1  1/344 (0.29%)  0/345 (0.00%) 
Bile duct obstruction * 1  0/344 (0.00%)  1/345 (0.29%) 
Cholangitis acute * 1  1/344 (0.29%)  0/345 (0.00%) 
Hepatotoxicity * 1  1/344 (0.29%)  0/345 (0.00%) 
Immune system disorders     
Anaphylactic reaction * 1  0/344 (0.00%)  1/345 (0.29%) 
Infections and infestations     
Bacteraemia * 1  0/344 (0.00%)  1/345 (0.29%) 
Biliary sepsis * 1  0/344 (0.00%)  1/345 (0.29%) 
Cellulitis * 1  0/344 (0.00%)  1/345 (0.29%) 
Cellulitis orbital * 1  0/344 (0.00%)  1/345 (0.29%) 
Device related infection * 1  0/344 (0.00%)  1/345 (0.29%) 
Diverticulitis * 1  1/344 (0.29%)  1/345 (0.29%) 
Gallbladder abscess * 1  0/344 (0.00%)  1/345 (0.29%) 
Herpes zoster * 1  1/344 (0.29%)  0/345 (0.00%) 
Infection * 1  1/344 (0.29%)  0/345 (0.00%) 
Kidney infection * 1  2/344 (0.58%)  0/345 (0.00%) 
Pneumonia * 1  1/344 (0.29%)  0/345 (0.00%) 
Pyelonephritis * 1  3/344 (0.87%)  3/345 (0.87%) 
Pyelonephritis acute * 1  1/344 (0.29%)  1/345 (0.29%) 
Sepsis * 1  4/344 (1.16%)  1/345 (0.29%) 
Tracheobronchitis * 1  0/344 (0.00%)  1/345 (0.29%) 
Upper respiratory tract infection * 1  1/344 (0.29%)  0/345 (0.00%) 
Urinary tract infection * 1  16/344 (4.65%)  7/345 (2.03%) 
Urosepsis * 1  1/344 (0.29%)  2/345 (0.58%) 
Vascular device infection * 1  2/344 (0.58%)  0/345 (0.00%) 
Injury, poisoning and procedural complications     
Cervical vertebral fracture * 1  1/344 (0.29%)  0/345 (0.00%) 
Chest injury * 1  1/344 (0.29%)  0/345 (0.00%) 
Contusion * 1  1/344 (0.29%)  0/345 (0.00%) 
Fall * 1  1/344 (0.29%)  0/345 (0.00%) 
Fractured sacrum * 1  1/344 (0.29%)  0/345 (0.00%) 
Infusion related reaction * 1  4/344 (1.16%)  0/345 (0.00%) 
Road traffic accident * 1  1/344 (0.29%)  0/345 (0.00%) 
Stomal hernia * 1  1/344 (0.29%)  0/345 (0.00%) 
Subdural haematoma * 1  1/344 (0.29%)  0/345 (0.00%) 
Urinary tract stoma complication * 1  0/344 (0.00%)  1/345 (0.29%) 
Investigations     
Blood creatine phosphokinase increased * 1  2/344 (0.58%)  0/345 (0.00%) 
Hepatic enzyme increased * 1  0/344 (0.00%)  1/345 (0.29%) 
Liver function test increased * 1  0/344 (0.00%)  1/345 (0.29%) 
Platelet count decreased * 1  1/344 (0.29%)  0/345 (0.00%) 
Troponin T increased * 1  1/344 (0.29%)  0/345 (0.00%) 
Metabolism and nutrition disorders     
Hypercalcaemia * 1  1/344 (0.29%)  0/345 (0.00%) 
Hyperkalaemia * 1  1/344 (0.29%)  0/345 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  3/344 (0.87%)  1/345 (0.29%) 
Bone pain * 1  1/344 (0.29%)  0/345 (0.00%) 
Flank pain * 1  1/344 (0.29%)  0/345 (0.00%) 
Muscular weakness * 1  1/344 (0.29%)  0/345 (0.00%) 
Musculoskeletal pain * 1  0/344 (0.00%)  1/345 (0.29%) 
Myositis * 1  1/344 (0.29%)  0/345 (0.00%) 
Pain in extremity * 1  1/344 (0.29%)  0/345 (0.00%) 
Pathological fracture * 1  0/344 (0.00%)  1/345 (0.29%) 
Synovial cyst * 1  0/344 (0.00%)  1/345 (0.29%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma gastric * 1  0/344 (0.00%)  1/345 (0.29%) 
Adenocarcinoma of colon * 1  0/344 (0.00%)  1/345 (0.29%) 
Basal cell carcinoma * 1  1/344 (0.29%)  2/345 (0.58%) 
Bladder cancer * 1  0/344 (0.00%)  1/345 (0.29%) 
Bladder transitional cell carcinoma * 1  0/344 (0.00%)  1/345 (0.29%) 
Malignant melanoma * 1  1/344 (0.29%)  0/345 (0.00%) 
Malignant melanoma in situ * 1  0/344 (0.00%)  1/345 (0.29%) 
Malignant neoplasm progression * 1  0/344 (0.00%)  1/345 (0.29%) 
Metastatic carcinoma of the bladder * 1  0/344 (0.00%)  1/345 (0.29%) 
Neoplasm progression * 1  0/344 (0.00%)  1/345 (0.29%) 
Oesophageal squamous cell carcinoma * 1  1/344 (0.29%)  0/345 (0.00%) 
Transitional cell carcinoma * 1  1/344 (0.29%)  0/345 (0.00%) 
Tumour pain * 1  0/344 (0.00%)  2/345 (0.58%) 
Nervous system disorders     
Cerebrovascular accident * 1  1/344 (0.29%)  1/345 (0.29%) 
Cognitive disorder * 1  1/344 (0.29%)  0/345 (0.00%) 
Headache * 1  0/344 (0.00%)  1/345 (0.29%) 
Ischaemic stroke * 1  0/344 (0.00%)  1/345 (0.29%) 
Seizure * 1  1/344 (0.29%)  1/345 (0.29%) 
Syncope * 1  0/344 (0.00%)  2/345 (0.58%) 
Product Issues     
Device occlusion * 1  1/344 (0.29%)  0/345 (0.00%) 
Psychiatric disorders     
Anxiety disorder * 1  0/344 (0.00%)  1/345 (0.29%) 
Depression * 1  1/344 (0.29%)  0/345 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  6/344 (1.74%)  6/345 (1.74%) 
Anuria * 1  0/344 (0.00%)  1/345 (0.29%) 
Bladder perforation * 1  0/344 (0.00%)  1/345 (0.29%) 
Haematuria * 1  5/344 (1.45%)  2/345 (0.58%) 
Haemorrhage urinary tract * 1  1/344 (0.29%)  0/345 (0.00%) 
Hydronephrosis * 1  3/344 (0.87%)  1/345 (0.29%) 
Nephritis * 1  1/344 (0.29%)  0/345 (0.00%) 
Renal impairment * 1  0/344 (0.00%)  1/345 (0.29%) 
Tubulointerstitial nephritis * 1  1/344 (0.29%)  0/345 (0.00%) 
Ureteric obstruction * 1  1/344 (0.29%)  0/345 (0.00%) 
Urinary tract obstruction * 1  0/344 (0.00%)  2/345 (0.58%) 
Reproductive system and breast disorders     
Pelvic pain * 1  1/344 (0.29%)  1/345 (0.29%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure * 1  1/344 (0.29%)  0/345 (0.00%) 
Chronic obstructive pulmonary disease * 1  0/344 (0.00%)  1/345 (0.29%) 
Dyspnoea * 1  2/344 (0.58%)  1/345 (0.29%) 
Interstitial lung disease * 1  1/344 (0.29%)  0/345 (0.00%) 
Pneumonitis * 1  1/344 (0.29%)  0/345 (0.00%) 
Pulmonary embolism * 1  1/344 (0.29%)  0/345 (0.00%) 
Respiratory distress * 1  1/344 (0.29%)  0/345 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  1/344 (0.29%)  0/345 (0.00%) 
Embolism * 1  1/344 (0.29%)  0/345 (0.00%) 
Hypotension * 1  1/344 (0.29%)  0/345 (0.00%) 
Orthostatic hypotension * 1  1/344 (0.29%)  0/345 (0.00%) 
1
Term from vocabulary, MedDRA v22.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Avelumab + Best Supportive Care (BSC) Best Supportive Care
Affected / at Risk (%) Affected / at Risk (%)
Total   313/344 (90.99%)   206/345 (59.71%) 
Blood and lymphatic system disorders     
Anaemia * 1  38/344 (11.05%)  21/345 (6.09%) 
Endocrine disorders     
Hyperthyroidism * 1  21/344 (6.10%)  1/345 (0.29%) 
Hypothyroidism * 1  40/344 (11.63%)  2/345 (0.58%) 
Gastrointestinal disorders     
Abdominal pain * 1  30/344 (8.72%)  22/345 (6.38%) 
Constipation * 1  54/344 (15.70%)  31/345 (8.99%) 
Diarrhoea * 1  57/344 (16.57%)  16/345 (4.64%) 
Nausea * 1  54/344 (15.70%)  22/345 (6.38%) 
Vomiting * 1  41/344 (11.92%)  12/345 (3.48%) 
General disorders     
Asthenia * 1  56/344 (16.28%)  19/345 (5.51%) 
Chills * 1  28/344 (8.14%)  3/345 (0.87%) 
Fatigue * 1  61/344 (17.73%)  23/345 (6.67%) 
Oedema peripheral * 1  22/344 (6.40%)  20/345 (5.80%) 
Pyrexia * 1  49/344 (14.24%)  11/345 (3.19%) 
Infections and infestations     
Influenza * 1  20/344 (5.81%)  10/345 (2.90%) 
Nasopharyngitis * 1  26/344 (7.56%)  13/345 (3.77%) 
Upper respiratory tract infection * 1  20/344 (5.81%)  8/345 (2.32%) 
Urinary tract infection * 1  49/344 (14.24%)  31/345 (8.99%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  31/344 (9.01%)  0/345 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  18/344 (5.23%)  2/345 (0.58%) 
Amylase increased * 1  23/344 (6.69%)  3/345 (0.87%) 
Blood creatinine increased * 1  22/344 (6.40%)  4/345 (1.16%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  47/344 (13.66%)  23/345 (6.67%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  56/344 (16.28%)  19/345 (5.51%) 
Back pain * 1  54/344 (15.70%)  33/345 (9.57%) 
Myalgia * 1  29/344 (8.43%)  10/345 (2.90%) 
Pain in extremity * 1  18/344 (5.23%)  21/345 (6.09%) 
Nervous system disorders     
Dizziness * 1  22/344 (6.40%)  12/345 (3.48%) 
Headache * 1  24/344 (6.98%)  8/345 (2.32%) 
Psychiatric disorders     
Insomnia * 1  21/344 (6.10%)  8/345 (2.32%) 
Renal and urinary disorders     
Haematuria * 1  35/344 (10.17%)  35/345 (10.14%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  44/344 (12.79%)  16/345 (4.64%) 
Dyspnoea * 1  21/344 (6.10%)  10/345 (2.90%) 
Skin and subcutaneous tissue disorders     
Dry skin * 1  22/344 (6.40%)  3/345 (0.87%) 
Pruritus * 1  59/344 (17.15%)  6/345 (1.74%) 
Rash * 1  40/344 (11.63%)  4/345 (1.16%) 
1
Term from vocabulary, MedDRA v22.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 8007181021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02603432    
Other Study ID Numbers: B9991001
2015-003262-86 ( EudraCT Number )
JAVELIN BLADDER 100 ( Other Identifier: Alias Study Number )
First Submitted: November 9, 2015
First Posted: November 11, 2015
Results First Submitted: October 16, 2020
Results First Posted: December 17, 2020
Last Update Posted: February 8, 2021