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

• ClinicalTrials.gov Identifier: NCT02603432
• Recruitment Status: Completed
• First Posted: November 11, 2015
• Results First Posted: December 17, 2020
• Last Update Posted: March 27, 2024
• Sponsor: Pfizer
• 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

Participant Flow

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
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	16	1
Not Completed	334	349
Reason Not Completed
Adverse Event	1	0
Death	221	242
Lost to Follow-up	3	9
Progressive Disease	7	5
Withdrawal by Subject	12	18
No Longer Meets Eligibility Criteria	3	0
Study terminated by sponsor	74	75
Other	13	0

Baseline Characteristics

Arm/Group Title		Avelumab + Best Supportive Care (BSC)	Best Supportive Care	Total
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
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%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
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 (for a maximum duration of 41 months)

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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)

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)
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 (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 millimeters. 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 (for a maximum duration of 41 months)

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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
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 (for a maximum duration of 41 months)

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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)
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 (for a maximum duration of 41 months)

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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
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 (for a maximum duration of 41 months)

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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)
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) (for a maximum duration of 41 months)

Outcome Measure Data

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
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
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) (for a maximum duration of 41 months)

Outcome Measure Data

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
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)
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 (for a maximum duration of 41 months)

Outcome Measure Data

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
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
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 (for a maximum duration of 41 months)

Outcome Measure Data

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
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)
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 (for a maximum duration of 41 months)

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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
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 (for a maximum duration of 41 months)

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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
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: Day1 up to 90 days after last dose of study drug; for BSC group: Day1 up to 90 days after EOT visit (for a maximum duration of up to approximately 70 months for both groups)

Outcome Measure Data

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 Cycle 1 Day (C1D1) on arm 'BSC'.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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
Grade 1	37 10.8%	76 22.0%
Grade 2	113 32.8%	104 30.1%
Grade 3	163 47.4%	58 16.8%
Grade 4	18 5.2%	8 2.3%
Grade 5	7 2.0%	24 7.0%

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
Description	Hematology (Anemia G3: hemoglobin<8.0 grams per deciliter [g/dL],<4.9 millimoles (mmol)/liter (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: Day1 up to 90 days after last dose of study drug; for BSC group: Day1 up to 90 days after EOT visit (for a maximum duration of up to approximately 70 months for both groups)

Outcome Measure Data

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'. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number analyzed (n)' = Participants evaluable for this outcome measure for each specified row.

Arm/Group Title		Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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
		16 4.7%	12 3.5%
Platelet Count Decreased	Number Analyzed	344 participants	339 participants
		3 0.9%	1 0.3%
Lymphocyte Count Decreased	Number Analyzed	344 participants	339 participants
		20 5.8%	11 3.2%
Neutrophil Count Decreased	Number Analyzed	344 participants	339 participants
		7 2.0%	0 0.0%
Creatinine Increased	Number Analyzed	344 participants	341 participants
		7 2.0%	5 1.5%
Serum Amylase Increased	Number Analyzed	340 participants	329 participants
		25 7.4%	9 2.7%
Lipase Increased	Number Analyzed	343 participants	332 participants
		37 10.8%	22 6.6%
ALT Increased	Number Analyzed	344 participants	341 participants
		11 3.2%	3 0.9%
AST Increased	Number Analyzed	344 participants	340 participants
		6 1.7%	3 0.9%
Blood Bilirubin Increased	Number Analyzed	344 participants	340 participants
		0 0.0%	3 0.9%
CPK Increased	Number Analyzed	339 participants	331 participants
		9 2.7%	0 0.0%
Hyperglycemia	Number Analyzed	344 participants	341 participants
		28 8.1%	16 4.7%

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
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 (Day [D] 1 of Cycle [C] 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7 , EOT visit (for a maximum duration of 41 months) (each cycle=28 days)

Outcome Measure Data

Analysis Population Description

Safety set analyzed. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified time points.

Arm/Group Title		Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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
Description	Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized.
Time Frame	Baseline (Day [D] 1 of Cycle [C] 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7 , EOT visit (for a maximum duration of 41 months) (each cycle=28 days)

Outcome Measure Data

Analysis Population Description

Safety set analyzed. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'Number analyzed' = participants evaluable for this outcome measure at specified time points.

Arm/Group Title		Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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
Description	The Lower Limit of Quantitation (LLQ) of avelumab was 0.20 micrograms (mcg)/milliliter (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 (each cycle=28 days)

Outcome Measure Data

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. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'n' signifies participants evaluable for this OM at specified time points.

Arm/Group Title		Avelumab + Best Supportive Care (BSC)
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
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 (each cycle=28 days)

Outcome Measure Data

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. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, 'n' signifies participants evaluable for this OM at specified time points.

Arm/Group Title		Avelumab + Best Supportive Care (BSC)
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
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 approximately 68 months)

Outcome Measure Data

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)
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-positive	66 19.2%

19. Secondary Outcome

Title	Number of ADA Ever Positive Participants For Each Serum of ADA Titers for Avelumab
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 131220) are reported.
Time Frame	From randomization up to the 30-Day Follow-up visit (maximum duration of up to approximately 68 months)

Outcome Measure Data

Analysis Population Description

The immunogenicity analysis set included 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)
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	19 28.8%
1620	10 15.2%
4860	11 16.7%
14580	7 10.6%
131220	1 1.5%

20. Secondary Outcome

Title	Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never Positive and Ever Positive Status
Description	nAb against avelumab in serum samples was determined and reported separately for nAb never positive and nAb ever positive participants. Participants were considered nAb ever-positive if they had at least one positive nAb result at any time point during study and were otherwise considered negative.
Time Frame	From randomization up to the 30-Day Follow-up visit (maximum duration of up to approximately 68 months)

Outcome Measure Data

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 nAb sample collected for avelumab in the avelumab containing arm.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)
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	284 82.6%
Ever-positive	60 17.4%

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)
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

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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)
Description	Number of Participants With CD8 T Lymphocytes (Cytotoxic T lymphocytes) were presented in this outcome.
Time Frame	Up to approximately 60 months

Outcome Measure Data

Analysis Population Description

Biomarker analysis set is a subset of the safety analysis set and included participants who have at least one baseline biomarker assessment performed. 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
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	326
Measure Type: Count of Participants; Unit of Measure: Participants
	148 43.9%	134 41.1%

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
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 (1 cycle=28 days)

Outcome Measure Data

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
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
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)

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants.

Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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.

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
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 (1 cycle=28 days)

Outcome Measure Data

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
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
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 (1 cycle=28 days)

Outcome Measure Data

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
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)

Adverse Events

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 70 months for both groups.
Adverse Event Reporting Description	Same event may appear as both non-SAE 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, SAEs and non-SAEs were assessed in Safety Analysis set.
Arm/Group Title	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
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	225/344 (65.41%)	242/345 (70.14%)
Serious Adverse Events
	Avelumab + Best Supportive Care (BSC)	Best Supportive Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	111/344 (32.27%)	73/345 (21.16%)
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%)
Angina pectoris * 1	1/344 (0.29%)	0/345 (0.00%)
Atrial fibrillation * 1	3/344 (0.87%)	1/345 (0.29%)
Atrial thrombosis * 1	1/344 (0.29%)	0/345 (0.00%)
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%)
Pleuropericarditis * 1	1/344 (0.29%)	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%)
Gastrointestinal disorders
Abdominal pain * 1	2/344 (0.58%)	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%)
Gastrointestinal haemorrhage * 1	0/344 (0.00%)	1/345 (0.29%)
Ileus * 1	3/344 (0.87%)	1/345 (0.29%)
Intestinal obstruction * 1	0/344 (0.00%)	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%)
Retroperitoneal haemorrhage * 1	1/344 (0.29%)	0/345 (0.00%)
Umbilical hernia * 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	4/344 (1.16%)	16/345 (4.64%)
Fatigue * 1	0/344 (0.00%)	1/345 (0.29%)
General physical health deterioration * 1	0/344 (0.00%)	1/345 (0.29%)
Hernia * 1	1/344 (0.29%)	0/345 (0.00%)
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%)
Biliary obstruction * 1	0/344 (0.00%)	1/345 (0.29%)
Cholangitis acute * 1	1/344 (0.29%)	0/345 (0.00%)
Cholecystitis 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%)
COVID-19 * 1	1/344 (0.29%)	0/345 (0.00%)
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	1/344 (0.29%)	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	1/344 (0.29%)	0/345 (0.00%)
Pneumonia * 1	1/344 (0.29%)	0/345 (0.00%)
Postoperative wound infection * 1	1/344 (0.29%)	0/345 (0.00%)
Pyelonephritis * 1	4/344 (1.16%)	4/345 (1.16%)
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	17/344 (4.94%)	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%)
Concussion * 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%)
Patella fracture * 1	1/344 (0.29%)	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	1/344 (0.29%)	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%)
SARS-CoV-2 test positive * 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%)
Hyperglycaemia * 1	1/344 (0.29%)	0/345 (0.00%)
Hyperkalaemia * 1	1/344 (0.29%)	0/345 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	0/344 (0.00%)	1/345 (0.29%)
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%)
Intervertebral disc protrusion * 1	1/344 (0.29%)	0/345 (0.00%)
Muscular weakness * 1	1/344 (0.29%)	0/345 (0.00%)
Myositis * 1	1/344 (0.29%)	0/345 (0.00%)
Osteoarthritis * 1	0/344 (0.00%)	2/345 (0.58%)
Pain in extremity * 1	2/344 (0.58%)	1/345 (0.29%)
Pathological fracture * 1	0/344 (0.00%)	1/345 (0.29%)
Spinal stenosis * 1	1/344 (0.29%)	0/345 (0.00%)
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%)
Anogenital warts * 1	1/344 (0.29%)	0/345 (0.00%)
Basal cell carcinoma * 1	1/344 (0.29%)	1/345 (0.29%)
Bladder cancer * 1	0/344 (0.00%)	1/345 (0.29%)
Bladder neoplasm * 1	1/344 (0.29%)	0/345 (0.00%)
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%)
Polycythaemia vera * 1	0/344 (0.00%)	1/345 (0.29%)
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
Cerebral infarction * 1	1/344 (0.29%)	0/345 (0.00%)
Cerebrovascular accident * 1	1/344 (0.29%)	1/345 (0.29%)
Cognitive disorder * 1	1/344 (0.29%)	0/345 (0.00%)
Headache * 1	1/344 (0.29%)	1/345 (0.29%)
Seizure * 1	1/344 (0.29%)	1/345 (0.29%)
Syncope * 1	0/344 (0.00%)	2/345 (0.58%)
Transient ischaemic attack * 1	1/344 (0.29%)	0/345 (0.00%)
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%)
Confusional state * 1	1/344 (0.29%)	0/345 (0.00%)
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%)
Cystitis haemorrhagic * 1	1/344 (0.29%)	0/345 (0.00%)
Haematuria * 1	5/344 (1.45%)	2/345 (0.58%)
Haemorrhage urinary tract * 1	1/344 (0.29%)	0/345 (0.00%)
Hydronephrosis * 1	4/344 (1.16%)	1/345 (0.29%)
Immune-mediated nephritis * 1	1/344 (0.29%)	0/345 (0.00%)
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 bladder haemorrhage * 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
Cystocele * 1	0/344 (0.00%)	1/345 (0.29%)
Pelvic pain * 1	1/344 (0.29%)	1/345 (0.29%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema * 1	1/344 (0.29%)	0/345 (0.00%)
Acute respiratory failure * 1	1/344 (0.29%)	0/345 (0.00%)
Chronic obstructive pulmonary disease * 1	2/344 (0.58%)	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%)	1/345 (0.29%)
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%)
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 v26.0; * Indicates events were collected by non-systematic assessment
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	321/344 (93.31%)	214/345 (62.03%)
Blood and lymphatic system disorders
Anaemia * 1	47/344 (13.66%)	22/345 (6.38%)
Endocrine disorders
Hyperthyroidism * 1	21/344 (6.10%)	1/345 (0.29%)
Hypothyroidism * 1	44/344 (12.79%)	2/345 (0.58%)
Gastrointestinal disorders
Abdominal pain * 1	34/344 (9.88%)	23/345 (6.67%)
Constipation * 1	60/344 (17.44%)	34/345 (9.86%)
Diarrhoea * 1	63/344 (18.31%)	17/345 (4.93%)
Nausea * 1	55/344 (15.99%)	22/345 (6.38%)
Vomiting * 1	45/344 (13.08%)	12/345 (3.48%)
General disorders
Asthenia * 1	64/344 (18.60%)	19/345 (5.51%)
Chills * 1	29/344 (8.43%)	3/345 (0.87%)
Fatigue * 1	66/344 (19.19%)	23/345 (6.67%)
Influenza like illness * 1	20/344 (5.81%)	4/345 (1.16%)
Oedema peripheral * 1	24/344 (6.98%)	21/345 (6.09%)
Pyrexia * 1	56/344 (16.28%)	12/345 (3.48%)
Infections and infestations
Influenza * 1	23/344 (6.69%)	11/345 (3.19%)
Nasopharyngitis * 1	33/344 (9.59%)	13/345 (3.77%)
Upper respiratory tract infection * 1	24/344 (6.98%)	8/345 (2.32%)
Urinary tract infection * 1	53/344 (15.41%)	33/345 (9.57%)
Injury, poisoning and procedural complications
Infusion related reaction * 1	30/344 (8.72%)	0/345 (0.00%)
Investigations
Alanine aminotransferase increased * 1	19/344 (5.52%)	3/345 (0.87%)
Amylase increased * 1	24/344 (6.98%)	3/345 (0.87%)
Blood creatine phosphokinase increased * 1	18/344 (5.23%)	2/345 (0.58%)
Blood creatinine increased * 1	29/344 (8.43%)	6/345 (1.74%)
Lipase increased * 1	22/344 (6.40%)	1/345 (0.29%)
Metabolism and nutrition disorders
Decreased appetite * 1	48/344 (13.95%)	24/345 (6.96%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	68/344 (19.77%)	29/345 (8.41%)
Back pain * 1	57/344 (16.57%)	34/345 (9.86%)
Myalgia * 1	32/344 (9.30%)	10/345 (2.90%)
Pain in extremity * 1	20/344 (5.81%)	23/345 (6.67%)
Nervous system disorders
Dizziness * 1	23/344 (6.69%)	12/345 (3.48%)
Headache * 1	27/344 (7.85%)	9/345 (2.61%)
Psychiatric disorders
Insomnia * 1	24/344 (6.98%)	9/345 (2.61%)
Renal and urinary disorders
Haematuria * 1	38/344 (11.05%)	35/345 (10.14%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	49/344 (14.24%)	18/345 (5.22%)
Dyspnoea * 1	26/344 (7.56%)	11/345 (3.19%)
Skin and subcutaneous tissue disorders
Dry skin * 1	23/344 (6.69%)	3/345 (0.87%)
Pruritus * 1	64/344 (18.60%)	6/345 (1.74%)
Rash * 1	43/344 (12.50%)	5/345 (1.45%)
Vascular disorders
Hypertension * 1	22/344 (6.40%)	8/345 (2.32%)
1 Term from vocabulary, MedDRA v26.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte RJ, Huang B, Costa N, Blake-Haskins JA, Grivas P. Plain language summary of results from the JAVELIN Bladder 100 study: avelumab maintenance treatment for advanced urothelial cancer. Future Oncol. 2022 Jun;18(19):2361-2371. doi: 10.2217/fon-2021-1631. Epub 2022 Apr 13.

Tomita Y, Yamamoto Y, Tsuchiya N, Kanayama H, Eto M, Miyake H, Powles T, Yoshida M, Koide Y, Umeyama Y, di Pietro A, Uemura H. Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis. Int J Clin Oncol. 2022 Feb;27(2):383-395. doi: 10.1007/s10147-021-02067-8. Epub 2022 Jan 1.

Powles T, Sridhar SS, Loriot Y, Bellmunt J, Mu XJ, Ching KA, Pu J, Sternberg CN, Petrylak DP, Tambaro R, Dourthe LM, Alvarez-Fernandez C, Aarts M, di Pietro A, Grivas P, Davis CB. Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial. Nat Med. 2021 Dec;27(12):2200-2211. doi: 10.1038/s41591-021-01579-0. Epub 2021 Dec 10.

Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.

• 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: March 27, 2024