A Study Of Avelumab Alone Or In Combination With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum Resistant/Refractory Ovarian Cancer (JAVELIN Ovarian 200)

• ClinicalTrials.gov Identifier: NCT02580058
• Recruitment Status: Completed
• First Posted: October 20, 2015
• Results First Posted: November 19, 2019
• Last Update Posted: July 10, 2023
• 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: Ovarian Cancer
• Interventions: Biological: avelumab; Drug: PLD
• Enrollment: 566

Participant Flow

Recruitment Details
Pre-assignment Details	Data reported based on last participant last visit (LPLV) date (12 July 2022).

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Period Title: Overall Study
Started [1]	188	188	190
Treated [2]	187	182	177
Completed [3]	0	0	0
Not Completed	188	188	190
Reason Not Completed
Adverse Event	16	30	20
Death	4	4	5
Physician Decision	1	3	11
Other	5	1	3
Withdrawal by Subject	4	7	31
Global Deterioration of Health Status	19	18	24
No Longer Meets Eligibility Criteria	1	0	2
Progressive Disease	137	125	94
Non-Compliance With Study Drug	1	0	0
[1] This table included all randomized participants.; [2] Participants received at least 1 dose of study drug.; [3] Participants were considered completed when at least one drug of the combination is completed.

Baseline Characteristics

Arm/Group Title		Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)	Total
Arm/Group Description		Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.	Total of all reporting groups
Overall Number of Baseline Participants		188	188	190	566
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	188 participants	188 participants	190 participants	566 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	111 59.0%	124 66.0%	114 60.0%	349 61.7%
	>=65 years	77 41.0%	64 34.0%	76 40.0%	217 38.3%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	188 participants	188 participants	190 participants	566 participants
		61.0 (10.26)	59.5 (10.05)	60.4 (10.64)	60.3 (10.32)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	188 participants	188 participants	190 participants	566 participants
	Female	188 100.0%	188 100.0%	190 100.0%	566 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	188 participants	188 participants	190 participants	566 participants
	Hispanic or Latino	2 1.1%	3 1.6%	1 0.5%	6 1.1%
	Not Hispanic or Latino	176 93.6%	176 93.6%	183 96.3%	535 94.5%
	Unknown or Not Reported	10 5.3%	9 4.8%	6 3.2%	25 4.4%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	188 participants	188 participants	190 participants	566 participants
	Black or African American	2 1.1%	2 1.1%	6 3.2%	10 1.8%
	American Indian or Alaska Native	0 0.0%	0 0.0%	1 0.5%	1 0.2%
	Asian	34 18.1%	53 28.2%	46 24.2%	133 23.5%
	Native Hawaiian or Other Pacific Islander	1 0.5%	0 0.0%	0 0.0%	1 0.2%
	White	148 78.7%	133 70.7%	135 71.1%	416 73.5%
	Other	1 0.5%	0 0.0%	2 1.1%	3 0.5%
	Unknown	2 1.1%	0 0.0%	0 0.0%	2 0.4%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from the date of randomization to the date of death due to any cause. OS time was summarized by treatment arm using the Kaplan-Meier method.
Time Frame	From randomization until the date of first documented progression or date of deaths from any cause, whichever came first, assessed up to 30 months (based on cutoff date: 19 September 2018).

Outcome Measure Data

Analysis Population Description

The primary analyses of OS were performed based on the Full Analysis Set (FAS). The FAS included all participants who were randomized.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	188	188	190
Median (95% Confidence Interval); Unit of Measure: months
	11.8; (8.9 to 14.1)	15.7; (12.7 to 18.7)	13.1; (11.8 to 15.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Pegylated Liposomal Doxorubicin (PLD)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8253
	Comments	[Not Specified]
	Method	Log Rank
	Comments	1-sided
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.867 to 1.497
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Avelumab + PLD, Pegylated Liposomal Doxorubicin (PLD)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2082
	Comments	[Not Specified]
	Method	Log Rank
	Comments	1-sided
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.672 to 1.179
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Progression Free Survival (PFS) Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description	PFS is defined as the time from date of randomization to the date of the first documentation of progression of disease (PD) or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method. PFS based on BICR assessment was evaluated for this endpoint.
Time Frame	From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The primary analyses of PFS based on BICR assessment were performed using FAS. The FAS included all participants who were randomized.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	188	188	190
Median (95% Confidence Interval); Unit of Measure: months
	1.9; (1.8 to 1.9)	3.7; (3.3 to 5.1)	3.5; (2.1 to 4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Pegylated Liposomal Doxorubicin (PLD)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.9999
	Comments	[Not Specified]
	Method	Log Rank
	Comments	1-sided
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.68
	Confidence Interval	(2-Sided) 95%; 1.310 to 2.160
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Avelumab + PLD, Pegylated Liposomal Doxorubicin (PLD)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0301
	Comments	[Not Specified]
	Method	Log Rank
	Comments	1-sided
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.607 to 1.011
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Objective Response Rate (ORR) Based on BICR Assessment
Description	Percentage of participants achieved objective response (OR) based on BICR assessment is presented for this endpoint. OR is defined as a complete response (CR, disappearance of all target lesions) or partial response (PR, >=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met and before the first documentation of disease progression. Only tumor assessments performed on or before the start date of any further anti-cancer therapies are considered in the assessment of best overall response.
Time Frame	Tumor assessments as assessed by BICR were conducted at every 8 weeks from screening until documented disease progression (approximately up to 30 months); based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were randomized.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	188	188	190
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	3.7; (1.5 to 7.5)	13.3; (8.8 to 19.0)	4.2; (1.8 to 8.1)

4. Secondary Outcome

Title	ORR Based on Investigator Assessment
Description	Percentage of participants achieved OR based on investigator assessment is presented for this endpoint. OR is defined as a CR (disappearance of all target lesions) or PR (>=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. The ORR on each randomized treatment arm were estimated by dividing the number of participants with OR (CR or PR) by number of participants randomized to the respective treatment arm.
Time Frame	Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were randomized.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	188	188	190
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	5.3; (2.6 to 9.6)	18.6; (13.3 to 24.9)	9.5; (5.7 to 14.6)

5. Secondary Outcome

Title	PFS Based on Investigator Assessment According to RECIST Version 1.1
Description	PFS is defined as the time from date of randomization to the date of the first documentation of PD or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method.
Time Frame	From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were randomized.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	188	188	190
Median (95% Confidence Interval); Unit of Measure: month
	1.9; (1.8 to 1.9)	4.7; (3.7 to 6.0)	3.7; (3.5 to 5.4)

6. Secondary Outcome

Title	Duration of Response (DR) Based on BICR Assessment
Description	DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR [disappearance of all target lesions] or PR [>=30% decrease under the baseline of the sum of diameters of all target measurable lesions]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
Time Frame	Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were randomized. Number analyzed are participants with confirmed CR or PR in the FAS within each treatment group.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	7	25	8
Median (95% Confidence Interval); Unit of Measure: months
	9.2 [1]; (6.4 to NA)	8.5 [2]; (6.1 to NA)	13.1 [2]; (5.5 to NA)

[1]

The upper limit of 95% confidence interval (CI) was 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.

7. Secondary Outcome

Title	DR Based on Investigator Assessment
Description	DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR [disappearance of all target lesions] or PR [>=30% decrease under the baseline of the sum of diameters of all target measurable lesions]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
Time Frame	Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were randomized. Number analyzed are participants with confirmed CR or PR in the FAS within each treatment group.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	10	35	18
Median (95% Confidence Interval); Unit of Measure: months
	10.4 [1]; (3.7 to NA)	7.6; (5.6 to 9.1)	7.4; (3.6 to 11.2)

[1]

The upper limit of 95% CI was not estimable due to the small number of events.

8. Secondary Outcome

Title	Disease Control (DC) Rate Based on BICR Assessment
Description	Percentage of participants achieving DC based on BICR assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or stable disease (SD) according to the RECIST version 1.1.
Time Frame	Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were randomized.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	188	188	190
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	33.0; (26.3 to 40.2)	57.4; (50.0 to 64.6)	48.9; (41.6 to 56.3)

9. Secondary Outcome

Title	DC Rate Based on Investigator Assessment
Description	Percentage of participants achieving DC based on investigator assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or SD according to the RECIST version 1.1.
Time Frame	Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were randomized.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	188	188	190
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	34.0; (27.3 to 41.3)	61.7; (54.3 to 68.7)	54.7; (47.4 to 62.0)

10. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	An adverse event (AE) is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; progression of the malignancy under study. Treatment emergent AEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period.
Time Frame	From the time of the first dose of study treatment through a minimum of 30 days + last dose of study treatment, start day of new anti-cancer therapy -1 day (up to 70 months); based on cutoff date: 13 July 2022.

Outcome Measure Data

Analysis Population Description

Analysis is based on the safety analysis set. The safety analysis set included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	187	182	177
Measure Type: Count of Participants; Unit of Measure: Participants
TEAE	180 96.3%	180 98.9%	173 97.7%
Treatment emergent SAEs	72 38.5%	74 40.7%	51 28.8%

11. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities
Description	The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 4.03 were summarized: hematology (anemia, lymphocyte count decreased, neutrophil count decreased; and platelet count decreased) and chemistry laboratory tests (creatinine increased; serum amylase increased and lipase increased).
Time Frame	From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

'Number of Participants Analyzed' is based on the safety analysis set, which included all participants who received at least 1 dose of study treatment. 'Number Analyzed' included the number of participants in the safety analysis set who can be evaluated for CTCAE criteria for each parameter in each treatment group.

Arm/Group Title		Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:		Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed		187	182	177
Measure Type: Count of Participants; Unit of Measure: Participants
Anemia	Number Analyzed	186 participants	178 participants	172 participants
		135 72.6%	155 87.1%	144 83.7%
Lymphocyte count decreased	Number Analyzed	185 participants	178 participants	171 participants
		89 48.1%	148 83.1%	107 62.6%
Neutrophil count decreased	Number Analyzed	185 participants	177 participants	172 participants
		26 14.1%	80 45.2%	62 36.0%
Platelet count decreased	Number Analyzed	186 participants	178 participants	172 participants
		33 17.7%	48 27.0%	50 29.1%
Creatinine increased	Number Analyzed	186 participants	178 participants	172 participants
		154 82.8%	151 84.8%	120 69.8%
Serum amylase increased	Number Analyzed	180 participants	172 participants	161 participants
		43 23.9%	35 20.3%	27 16.8%
Lipase increased	Number Analyzed	175 participants	173 participants	159 participants
		27 15.4%	33 19.1%	21 13.2%

12. Secondary Outcome

Title	Change From Baseline in Vital Signs - Blood Pressure
Description	Vital signs included blood pressure and pulse rate. Changes from baseline in sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were summarized.
Time Frame	From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

'Number of Participants Analyzed' is based on the safety analysis set, which included all participants who received at least 1 dose of study treatment. 'Number Analyzed' included the number of participants in the safety analysis set with at least a baseline and post-baseline assessment at the visit.

Arm/Group Title		Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:		Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed		187	182	177
Mean (Standard Deviation); Unit of Measure: mm Hg
DBP Cycle 1 Day 15	Number Analyzed	180 participants	170 participants	142 participants
		0.1 (9.79)	-2.2 (9.12)	0.7 (8.89)
DBP Cycle 2 Day 1	Number Analyzed	164 participants	168 participants	156 participants
		-1.1 (9.61)	-2.8 (8.01)	-0.1 (9.34)
DBP Cycle 2 Day 15	Number Analyzed	138 participants	157 participants	124 participants
		0.1 (10.05)	-2.8 (9.19)	-0.1 (8.83)
DBP Cycle 3 Day 1	Number Analyzed	104 participants	141 participants	106 participants
		0 (10.81)	-2.7 (8.95)	-0.2 (8.96)
DBP Cycle 3 Day 15	Number Analyzed	95 participants	128 participants	84 participants
		-0.6 (9.25)	-2.3 (8.56)	-0.5 (8.67)
DBP End of Treatment	Number Analyzed	146 participants	138 participants	136 participants
		1.1 (10.87)	-0.3 (11.08)	0.8 (10.40)
SBP Cycle 1 Day 15	Number Analyzed	180 participants	170 participants	142 participants
		-0.9 (14.35)	-2.3 (13.12)	-1.0 (13.94)
SBP Cycle 2 Day 1	Number Analyzed	164 participants	168 participants	156 participants
		-2.2 (14.44)	-3.4 (13.70)	-2.8 (13.39)
SBP Cycle 2 Day 15	Number Analyzed	138 participants	157 participants	124 participants
		-0.6 (14.11)	-3.7 (14.78)	-1.8 (14.98)
SBP Cycle 3 Day 1	Number Analyzed	104 participants	141 participants	106 participants
		-0.2 (15.59)	-2.7 (14.36)	-1.5 (14.14)
SBP Cycle 3 Day 15	Number Analyzed	95 participants	128 participants	84 participants
		-0.2 (13.78)	-2.1 (15.30)	-2.2 (13.96)
SBP End of Treatment	Number Analyzed	146 participants	138 participants	136 participants
		-0.9 (17.21)	-1.0 (16.83)	-3.2 (15.92)

13. Secondary Outcome

Title	Change From Baseline in Vital Signs - Pulse Rate
Description	Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized.
Time Frame	From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

'Number of Participants Analyzed' is based on the safety analysis set, which included all participants who received at least 1 dose of study treatment. 'Number Analyzed' included the number of participants in the safety analysis set with at least a baseline and post-baseline assessment at the visit.

Arm/Group Title		Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:		Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed		187	182	177
Mean (Standard Deviation); Unit of Measure: bpm
Cycle 1 Day 15	Number Analyzed	180 participants	170 participants	142 participants
		2.9 (9.95)	1.8 (12.10)	3.5 (10.70)
Cycle 2 Day 1	Number Analyzed	164 participants	167 participants	155 participants
		2.6 (10.92)	2.9 (11.18)	1.7 (9.71)
Cycle 2 Day 15	Number Analyzed	138 participants	157 participants	124 participants
		2.9 (11.19)	3.5 (11.79)	3.2 (11.54)
Cycle 3 Day 1	Number Analyzed	104 participants	141 participants	106 participants
		2.4 (10.00)	2.1 (11.78)	1.4 (11.14)
Cycle 3 Day 15	Number Analyzed	95 participants	128 participants	84 participants
		3.0 (12.23)	1.4 (11.44)	2.4 (10.41)
End of Treatment	Number Analyzed	146 participants	138 participants	136 participants
		7.7 (14.27)	7.4 (13.70)	5.7 (14.10)

14. Secondary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Abnormalities
Description	Categorical summarization ECG criteria were as follows: 1) QT interval, QTcB, QTcF and QTcP: increase from baseline >30 ms or 60 ms; absolute value > 450 ms, >480 ms and > 500 ms; 2) heart rate (HR): change from baseline >=20 bpm and absolute value <=50 bpm or >=120 bpm; 3) PR interval: absolute value >=220 ms and increase from baseline >=20 ms; 4) QRS: >= 120 ms.
Time Frame	From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

'Number of Participants Analyzed' is based on the safety analysis set, which included all participants who received at least 1 dose of study treatment. 'Number Analyzed' included the number of participants in the safety analysis set who had a at least 1 post-baseline ECG assessment performed.

Arm/Group Title		Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:		Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed		187	182	177
Measure Type: Count of Participants; Unit of Measure: Participants
QT increase from baseline >30 ms	Number Analyzed	183 participants	176 participants	169 participants
		26 14.2%	40 22.7%	47 27.8%
QT increase from baseline >60 ms	Number Analyzed	183 participants	176 participants	169 participants
		5 2.7%	9 5.1%	4 2.4%
QT >450 ms	Number Analyzed	183 participants	176 participants	169 participants
		6 3.3%	10 5.7%	5 3.0%
QT >480 ms	Number Analyzed	183 participants	176 participants	169 participants
		1 0.5%	2 1.1%	2 1.2%
QT >500 ms	Number Analyzed	183 participants	176 participants	169 participants
		1 0.5%	1 0.6%	1 0.6%
QTcB increase from baseline >30 ms	Number Analyzed	154 participants	153 participants	143 participants
		33 21.4%	36 23.5%	22 15.4%
QTcB increase from baseline >60 ms	Number Analyzed	154 participants	153 participants	143 participants
		9 5.8%	7 4.6%	8 5.6%
QTcB >450 ms	Number Analyzed	161 participants	160 participants	145 participants
		56 34.8%	63 39.4%	45 31.0%
QTcB >480 ms	Number Analyzed	161 participants	160 participants	145 participants
		9 5.6%	19 11.9%	9 6.2%
QTcB >500 ms	Number Analyzed	161 participants	160 participants	145 participants
		5 3.1%	9 5.6%	5 3.4%
QTcF increase from baseline >30 ms	Number Analyzed	154 participants	153 participants	143 participants
		19 12.3%	24 15.7%	13 9.1%
QTcF increase from baseline >60 ms	Number Analyzed	154 participants	153 participants	143 participants
		6 3.9%	5 3.3%	5 3.5%
QTcF >450 ms	Number Analyzed	161 participants	160 participants	145 participants
		18 11.2%	27 16.9%	14 9.7%
QTcF >480 ms	Number Analyzed	161 participants	160 participants	145 participants
		4 2.5%	8 5.0%	5 3.4%
QTcF >500 ms	Number Analyzed	161 participants	160 participants	145 participants
		3 1.9%	2 1.3%	4 2.8%
QTcP increase from baseline >30 ms	Number Analyzed	154 participants	153 participants	143 participants
		17 11.0%	23 15.0%	12 8.4%
QTcP increase from baseline >60 ms	Number Analyzed	154 participants	153 participants	143 participants
		6 3.9%	5 3.3%	4 2.8%
QTcP >450 ms	Number Analyzed	161 participants	160 participants	145 participants
		19 11.8%	29 18.1%	17 11.7%
QTcP >480 ms	Number Analyzed	161 participants	160 participants	145 participants
		2 1.2%	7 4.4%	2 1.4%
QTcP >500 ms	Number Analyzed	161 participants	160 participants	145 participants
		1 0.6%	2 1.3%	2 1.4%
Heart rate <=50 bpm and decrease >= 20 bpm	Number Analyzed	154 participants	153 participants	143 participants
		0 0.0%	1 0.7%	0 0.0%
Heart rate >=120 bpm and increase >= 20 bpm	Number Analyzed	154 participants	153 participants	143 participants
		5 3.2%	5 3.3%	3 2.1%
PR >=220 ms and increase from baseline >=20 ms	Number Analyzed	182 participants	176 participants	168 participants
		3 1.6%	4 2.3%	2 1.2%
QRS >=120 ms	Number Analyzed	183 participants	176 participants	169 participants
		7 3.8%	9 5.1%	9 5.3%

15. Secondary Outcome

Title	Number of Participants With % Left Ventricular Ejection Fraction (LVEF) Decrease From Baseline
Description	LVEF decrease was summarized by multiple-gated acquisition (MUGA)/ echocardiogram (ECHO) parameter. Participants with a LVEF% >=10 points and >= 15 points decrease from baseline during the on-treatment period were summarized.
Time Frame	Screening, Cycle 3 Day 1 (repeated every 2 cycles) to the end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

'Number of Participants Analyzed' is based on number of participants in the safety analysis set with a baseline and a post-baseline assessment within each treatment group.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	129	154	132
Measure Type: Count of Participants; Unit of Measure: Participants
>= 10 point decrease from baseline	8 6.2%	22 14.3%	13 9.8%
>= 15 point decrease from baseline	3 2.3%	8 5.2%	3 2.3%

16. Secondary Outcome

Title	Number of Participants With PD-L1 Expression for PFS (Based on BICR Assessment) and for OS
Description	PD-L1 expression was assessed by immunohistochemistry. Participants were considered positive for PD-L1 if their baseline tissue sample demonstrated PD-L1 expression on >=1% of tumor cells or >=5% of immune cells.
Time Frame	Biomarkers are measured only at screening.

Outcome Measure Data

Analysis Population Description

The biomarker analysis set included participants who had at least 1 screening biomarker assessment. 'Number of Participants Analyzed' is based on number of participants in the biomarker analysis set within each treatment group with reported PD-L1 status.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	170	173	165
Measure Type: Count of Participants; Unit of Measure: Participants
	100 58.8%	100 57.8%	88 53.3%

17. Secondary Outcome

Title	Number of Participants With CD8 Expression for PFS (Based on BICR Assessment) and for OS
Description	Tumor infiltrating CD8 positive (CD8+) T lymphocytes was assessed by immunohistochemistry. Participants were considered positive for CD8 T cells if their baseline tissue sample demonstrated presence of >=1% CD8+ cells across the area of the tumor.
Time Frame	Biomarkers are measured only at screening.

Outcome Measure Data

Analysis Population Description

The biomarker analysis set included participants who had at least 1 screening biomarker assessment. 'Number of Participants Analyzed' is based on number of participants in the biomarker analysis set within each treatment group with reported CD8 status.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	165	171	164
Measure Type: Count of Participants; Unit of Measure: Participants
	76 46.1%	80 46.8%	72 43.9%

18. Secondary Outcome

Title	Number of Participants With Improved, Stable and Deterioration Based on 10-Point Change for EORTC QLQ-C30 Global QoL
Description	The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) is a 30 question survey and includes 5 functional domain subscales, global health status/quality of life, disease/treatment related symptoms, and the perceived financial impact of disease. Higher scores are reflective of a greater presence of symptoms.
Time Frame	Day 1 of Cycle 1, Day 1 of each subsequent cycle, end of treatment/withdrawal visit and the 30, 60 and 90 days safety follow up visits, based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The analysis is based on the FAS. The FAS included all participants who were randomized. 'Number Analyzed' in represents number of participants in the FAS with a score at baseline and post-baseline.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	152	166	148
Measure Type: Count of Participants; Unit of Measure: Participants
Deterioration	46 30.3%	65 39.2%	46 31.1%
Improved	23 15.1%	20 12.0%	26 17.6%
Stable	83 54.6%	81 48.8%	76 51.4%

19. Secondary Outcome

Title	Time to Deterioration in Abdominal/GI Symptom Subscale of EORTC QLQ-OV28
Description	The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28 item instrument with 7 functional domain subscales. Time to deterioration was defined as the time from randomization to the first time the participant's score showed a 15-point or higher increase in the score of the abdominal/GI symptom subscale of the EORTC QLQ-OV28.
Time Frame	From Day 1 of Cycle 1 to prior to end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.

Outcome Measure Data

Analysis Population Description

The analysis is based on the FAS. The FAS included all participants who were randomized.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	188	188	190
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	11.1 [2]; (6.5 to NA)	10.6 [2]; (9.2 to NA)

[1]

The median estimates of time to event, upper and lower limits 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.

20. Secondary Outcome

Title	Change From Baseline in EQ-VAS Score at End of Treatment
Description	The EuroQol- 5 Dimensions- 5 Levels (EQ-5D-5L) questionnaire consists of the EQ-5D-5L descriptive system and a visual analogue scale (the EuroQol-visual analogue scale [EQ-VAS]). The respondent's self-rated health is assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS.
Time Frame	Baseline and end of treatment/withdrawal visit

Outcome Measure Data

Analysis Population Description

The analysis is based on the FAS. The FAS included all participants who were randomized. 'Number Analyzed' represents number of participants in the FAS with an assessment at the visit or with at least a baseline and post-baseline assessment at visit.

Arm/Group Title	Avelumab	Avelumab + PLD	Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Number of Participants Analyzed	111	116	111
Mean (Standard Deviation); Unit of Measure: scores on a scale
	-13.6 (20.56)	-11.2 (19.79)	-7.7 (22.26)

21. Secondary Outcome

Title	Serum Trough Concentration (Ctrough) For Avelumab Following Cycle 2 Day 1 Pegylated Liposomal Doxorubicin (PLD) Dose
Description	Ctrough was defined as predose concentration during multiple dosing, and can be observed directly from data.
Time Frame	At predose (0 H) on Cycle 2 Day 1

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as participants in the safety analysis set who had at least 1 post-dose concentration measurement above the lower limit of quantitation (LLQ) for avelumab.

Arm/Group Title	Avelumab	Avelumab + PLD
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.
Overall Number of Participants Analyzed	136	139
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: microgram per milliliter (mcg/mL)
	21.1; (89%)	23.19; (74%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Avelumab + PLD
	Comments	Avelumab was the Reference treatment and Avelumab + PLD was the Test treatment
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (Test/Reference, %)
	Estimated Value	110
	Confidence Interval	(2-Sided) 90%; 95.4 to 126.7
	Estimation Comments	[Not Specified]

22. Secondary Outcome

Title	Serum Maximum Concentration (Cmax) For Avelumab Following Cycle 2 Day 1 PLD Dose
Description	Cmax was defined as maximum observed serum concentration, and can be observed directly from data.
Time Frame	At postdose (end of infusion, 1H) on Cycle 2 Day 1

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as participants in the safety analysis set who had at least 1 post-dose concentration measurement above the LLQ for avelumab.

Arm/Group Title	Avelumab	Avelumab + PLD
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.
Overall Number of Participants Analyzed	104	110
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg/mL
	231.6; (43%)	207.9; (71%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avelumab, Avelumab + PLD
	Comments	Avelumab was the Reference treatment and Avelumab + PLD was the Test treatment
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (Test/Reference, %)
	Estimated Value	90
	Confidence Interval	(2-Sided) 90%; 79.5 to 101.5
	Estimation Comments	[Not Specified]

23. Secondary Outcome

Title	Cmax For Doxorubicin Following Cycle 2 Day 1 PLD Dose
Description	Cmax was defined as maximum observed serum concentration, and can be observed directly from data.
Time Frame	From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as a subset of the safety analysis set and included patients who had at least one of the PK parameters of interest for doxorubicin.

Arm/Group Title	Pegylated Liposomal Doxorubicin (PLD)	Avelumab + PLD
Arm/Group Description:	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.
Overall Number of Participants Analyzed	15	15
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram per milliliter (ng/mL)
	26810; (14%)	25850; (17%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pegylated Liposomal Doxorubicin (PLD), Avelumab + PLD
	Comments	PLD was the Reference treatment and Avelumab + PLD was the Test treatment.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (Test/Reference, %)
	Estimated Value	96
	Confidence Interval	(2-Sided) 90%; 87 to 106
	Estimation Comments	[Not Specified]

24. Secondary Outcome

Title	Area Under The Concentration Time Profile From Time Zero to 24 Hours (AUC24) For Doxorubicin Following Cycle 2 Day 1 PLD Dose
Description	AUC24 was defined as area under the concentration time profile from time zero to 24 hours.
Time Frame	From 0 through 24 hours postdose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as a subset of the safety analysis set and included patients who had at least one of the PK parameters of interest for doxorubicin.

Arm/Group Title	Pegylated Liposomal Doxorubicin (PLD)	Avelumab + PLD
Arm/Group Description:	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.
Overall Number of Participants Analyzed	14	14
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram*hour per milliliter (ng*hr/mL)
	567600; (11%)	541700; (14%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pegylated Liposomal Doxorubicin (PLD), Avelumab + PLD
	Comments	PLD was the Reference treatment and Avelumab + PLD was the Test treatment.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (Test/Reference, %)
	Estimated Value	95
	Confidence Interval	(2-Sided) 90%; 88 to 104
	Estimation Comments	[Not Specified]

25. Secondary Outcome

Title	Area Under The Concentration Time Profile From Time Zero to 336 Hours (AUC336) For Doxorubicin Following Cycle 2 Day 1 PLD Dose
Description	AUC336 was defined as area under the concentration time profile from time zero to 336 hours.
Time Frame	From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as a subset of the safety analysis set and included patients who had at least one of the PK parameters of interest for doxorubicin.

Arm/Group Title	Pegylated Liposomal Doxorubicin (PLD)	Avelumab + PLD
Arm/Group Description:	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.
Overall Number of Participants Analyzed	13	12
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*hr/mL
	2848000; (20%)	2571000; (30%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pegylated Liposomal Doxorubicin (PLD), Avelumab + PLD
	Comments	PLD was the Reference treatment and Avelumab + PLD was the Test treatment.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (Test/Reference, %)
	Estimated Value	90
	Confidence Interval	(2-Sided) 90%; 76 to 107
	Estimation Comments	[Not Specified]

26. Secondary Outcome

Title	Area Under The Concentration Time Profile From Time Zero to The Last Quantifiable Concentration (AUClast) For Doxorubicin Following Cycle 2 Day 1 PLD Dose
Description	AUClast was defined as area under the concentration time profile from time zero to the time of the last quantifiable concentration (Clast).
Time Frame	From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose

Outcome Measure Data

Analysis Population Description

The PK parameter analysis set was defined as a subset of the safety analysis set and included patients who had at least one of the PK parameters of interest for doxorubicin.

Arm/Group Title	Pegylated Liposomal Doxorubicin (PLD)	Avelumab + PLD
Arm/Group Description:	PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.
Overall Number of Participants Analyzed	15	15
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*hr/mL
	2043000; (119%)	2052000; (71%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pegylated Liposomal Doxorubicin (PLD), Avelumab + PLD
	Comments	PLD was the Reference treatment and Avelumab + PLD was the Test treatment.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Mean Ratio (Test/Reference, %)
	Estimated Value	100
	Confidence Interval	(2-Sided) 90%; 60 to 168
	Estimation Comments	[Not Specified]

27. Secondary Outcome

Title	Number of Participants With Treatment-Boosted Anti-Drug Antibody (ADA)
Description	Treatment-boosted ADA was defined as a positive ADA result at baseline and the titer ≥ 8×baseline titer at least once after treatment with avelumab.
Time Frame	At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab

Outcome Measure Data

Analysis Population Description

The analysis set was defined as participants with valid baseline ADA results and at least one valid post-baseline ADA result in the immunogenicity analysis set. The immunogenicity analysis set was a subset of the safety analysis set and included patients who had at least one ADA/nAb sample collected for avelumab in the avelumab containing arms.

Arm/Group Title	Avelumab	Avelumab + PLD	All Participants
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	Total participants from the 2 arms.
Overall Number of Participants Analyzed	165	167	332
Measure Type: Count of Participants; Unit of Measure: Participants
	1 0.6%	0 0.0%	1 0.3%

28. Secondary Outcome

Title	Number of Participants With Treatment-Induced ADA
Description	Treatment-induced ADA was defined as participant who was ADA-negative at baseline and has at least one positive post-baseline ADA result; or if participant did not have a baseline sample, the participant had at least one positive past-baseline ADA result.
Time Frame	At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab

Outcome Measure Data

Analysis Population Description

The analysis set was defined as participants with at least 1 valid post-baseline ADA results and without positive baseline ADA result in the immunogenicity analysis set. The immunogenicity analysis set was a subset of the safety analysis set and included patients who had at least one ADA/nAb sample collected for avelumab in the avelumab containing arms.

Arm/Group Title	Avelumab	Avelumab + PLD	All Participants
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	Total participants from the 2 arms.
Overall Number of Participants Analyzed	169	167	336
Measure Type: Count of Participants; Unit of Measure: Participants
	27 16.0%	2 1.2%	29 8.6%

29. Secondary Outcome

Title	Number of Participants With Treatment-Induced Neutralizing Antibody (nAb)
Description	Treatment-induced nAb was defined as participant who was not nAb positive at baseline and had at least one positive post-baseline nAb result; or if participant did not have a baseline sample, the participant had at least one positive past-baseline ADA result.
Time Frame	At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab

Outcome Measure Data

Analysis Population Description

The analysis set was defined as participants with at least 1 valid post-baseline ADA result and without positive baseline nAb result in the immunogenicity analysis set. The immunogenicity analysis set was a subset of the safety analysis set and included patients who had at least one ADA/nAb sample collected for avelumab in the avelumab containing arms.

Arm/Group Title	Avelumab	Avelumab + PLD	All Participants
Arm/Group Description:	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.	Total participants from the 2 arms.
Overall Number of Participants Analyzed	173	169	342
Measure Type: Count of Participants; Unit of Measure: Participants
	5 2.9%	1 0.6%	6 1.8%

Adverse Events

Time Frame	AEs (serious and non-serious) should be reported from the time of the first dose of study treatment through a minimum of 30 days + last dose of study treatment, start day of new anti-cancer therapy -1 day (up to 70 months). Based on the cutoff: 13 July 2022.
Adverse Event Reporting Description	The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. The mortality analysis set included all randomized participants. The AE and SAE analysis set included participants who received at least 1 dose of study drug.
Arm/Group Title	Avelumab		Avelumab + PLD		Pegylated Liposomal Doxorubicin (PLD)
Arm/Group Description	Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.		Avelumab 10 mg/kg given as a 1-hour IV Q2W in 4-week cycles + pegylated liposomal doxorubicin (PLD) 40 mg/square meter given as a 1-hour IV infusion every 4 weeks (Q4W) in 4-week cycles.		PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
All-Cause Mortality
	Avelumab		Avelumab + PLD		Pegylated Liposomal Doxorubicin (PLD)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	122/187 (65.24%)		107/182 (58.79%)		116/177 (65.54%)
Serious Adverse Events
	Avelumab		Avelumab + PLD		Pegylated Liposomal Doxorubicin (PLD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/187 (38.50%)		74/182 (40.66%)		51/177 (28.81%)
Blood and lymphatic system disorders
Anaemia * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Febrile neutropenia * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	3/177 (1.69%)	3
Neutropenia * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Thrombocytopenia * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	1/177 (0.56%)	1
Cardiac disorders
Atrial fibrillation * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Myocardial infarction * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Endocrine disorders
Basedow's disease * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Hypopituitarism * 1	0/187 (0.00%)	0	2/182 (1.10%)	2	0/177 (0.00%)	0
Glucocorticoid deficiency * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Eye disorders
Retinal detachment * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Gastrointestinal disorders
Abdominal distension * 1	3/187 (1.60%)	3	1/182 (0.55%)	1	1/177 (0.56%)	1
Abdominal pain * 1	9/187 (4.81%)	10	6/182 (3.30%)	6	6/177 (3.39%)	6
Abdominal pain upper * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	1/177 (0.56%)	1
Ascites * 1	2/187 (1.07%)	3	1/182 (0.55%)	2	1/177 (0.56%)	1
Colitis * 1	0/187 (0.00%)	0	1/182 (0.55%)	3	0/177 (0.00%)	0
Constipation * 1	2/187 (1.07%)	2	5/182 (2.75%)	5	1/177 (0.56%)	1
Diarrhoea * 1	4/187 (2.14%)	4	1/182 (0.55%)	1	1/177 (0.56%)	1
Faecaloma * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Haematemesis * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Ileus * 1	1/187 (0.53%)	1	4/182 (2.20%)	4	2/177 (1.13%)	2
Intestinal obstruction * 1	11/187 (5.88%)	16	9/182 (4.95%)	9	6/177 (3.39%)	6
Intestinal pseudo-obstruction * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Intussusception * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Large intestinal obstruction * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Malignant gastrointestinal obstruction * 1	1/187 (0.53%)	1	1/182 (0.55%)	1	1/177 (0.56%)	1
Mechanical ileus * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Nausea * 1	7/187 (3.74%)	7	4/182 (2.20%)	4	1/177 (0.56%)	1
Obstruction gastric * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Oesophagitis * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Pancreatitis acute * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Small intestinal obstruction * 1	5/187 (2.67%)	5	4/182 (2.20%)	4	2/177 (1.13%)	2
Stomatitis * 1	0/187 (0.00%)	0	2/182 (1.10%)	2	1/177 (0.56%)	1
Subileus * 1	1/187 (0.53%)	1	1/182 (0.55%)	1	2/177 (1.13%)	2
Umbilical hernia * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Vomiting * 1	7/187 (3.74%)	8	4/182 (2.20%)	4	3/177 (1.69%)	5
Proctalgia * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
General disorders
Administration site extravasation * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Asthenia * 1	0/187 (0.00%)	0	2/182 (1.10%)	2	0/177 (0.00%)	0
Chest discomfort * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Chills * 1	1/187 (0.53%)	1	1/182 (0.55%)	1	0/177 (0.00%)	0
Complication associated with device * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Disease progression * 1	10/187 (5.35%)	10	5/182 (2.75%)	5	2/177 (1.13%)	2
Fatigue * 1	0/187 (0.00%)	0	2/182 (1.10%)	2	0/177 (0.00%)	0
General physical health deterioration * 1	2/187 (1.07%)	2	2/182 (1.10%)	2	0/177 (0.00%)	0
Influenza like illness * 1	1/187 (0.53%)	2	0/182 (0.00%)	0	0/177 (0.00%)	0
Localised oedema * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Malaise * 1	0/187 (0.00%)	0	2/182 (1.10%)	2	0/177 (0.00%)	0
Mucosal inflammation * 1	0/187 (0.00%)	0	1/182 (0.55%)	2	0/177 (0.00%)	0
Oedema peripheral * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Pain * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Pyrexia * 1	7/187 (3.74%)	8	8/182 (4.40%)	9	1/177 (0.56%)	3
Hepatobiliary disorders
Autoimmune hepatitis * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Drug-induced liver injury * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Hepatic failure * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Immune system disorders
Anaphylactic reaction * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Cytokine release syndrome * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Hypersensitivity * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Immune-mediated adverse reaction * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Infections and infestations
Bacteraemia * 1	1/187 (0.53%)	1	1/182 (0.55%)	1	0/177 (0.00%)	0
Cellulitis * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Cholangitis infective * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Cystitis * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Device related infection * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Erysipelas * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Gastroenteritis * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	1/177 (0.56%)	1
Infectious pleural effusion * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Influenza * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	2/177 (1.13%)	2
Lymph gland infection * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Medical device site infection * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Meningitis * 1	0/187 (0.00%)	0	1/182 (0.55%)	2	0/177 (0.00%)	0
Nail infection * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Oral fungal infection * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Peritonitis * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Peritonitis bacterial * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Pneumonia * 1	3/187 (1.60%)	3	3/182 (1.65%)	3	0/177 (0.00%)	0
Pyelonephritis * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	1/177 (0.56%)	1
Respiratory tract infection * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Sepsis * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	2/177 (1.13%)	3
Septic pulmonary embolism * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Septic shock * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Sinusitis * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Staphylococcal infection * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	1/177 (0.56%)	1
Urinary tract infection * 1	1/187 (0.53%)	1	1/182 (0.55%)	1	2/177 (1.13%)	2
Urosepsis * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Viral upper respiratory tract infection * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
COVID-19 pneumonia * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Device related bacteraemia * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	1/177 (0.56%)	1
Pneumonia aspiration * 1	1/187 (0.53%)	2	0/182 (0.00%)	0	0/177 (0.00%)	0
Vascular device infection * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	1/177 (0.56%)	1
Injury, poisoning and procedural complications
Infusion related reaction * 1	1/187 (0.53%)	1	3/182 (1.65%)	3	1/177 (0.56%)	1
Patella fracture * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Stoma complication * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Upper limb fracture * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Vascular access complication * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Investigations
Aspartate aminotransferase increased * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Blood creatine phosphokinase increased * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Haemoglobin decreased * 1	1/187 (0.53%)	2	0/182 (0.00%)	0	0/177 (0.00%)	0
Neutrophil count decreased * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Urine output decreased * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
White blood cell count decreased * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Metabolism and nutrition disorders
Decreased appetite * 1	3/187 (1.60%)	3	1/182 (0.55%)	1	1/177 (0.56%)	1
Dehydration * 1	2/187 (1.07%)	2	1/182 (0.55%)	1	1/177 (0.56%)	1
Hypercalcaemia * 1	0/187 (0.00%)	0	5/182 (2.75%)	6	1/177 (0.56%)	3
Hypokalaemia * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Hypomagnesaemia * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Hyponatraemia * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	2/177 (1.13%)	2
Musculoskeletal and connective tissue disorders
Back pain * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	2/177 (1.13%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Nervous system disorders
Aphasia * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Clonic convulsion * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Tremor * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Product Issues
Device dislocation * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Psychiatric disorders
Confusional state * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	1/177 (0.56%)	1
Mental status changes * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Renal and urinary disorders
Acute kidney injury * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Chronic kidney disease * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Haematuria * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Obstructive nephropathy * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Renal failure * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Urinary tract obstruction * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Reproductive system and breast disorders
Vaginal haemorrhage * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Dyspnoea * 1	3/187 (1.60%)	3	5/182 (2.75%)	7	0/177 (0.00%)	0
Lung disorder * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	2
Oropharyngeal pain * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Pleural effusion * 1	2/187 (1.07%)	3	0/182 (0.00%)	0	0/177 (0.00%)	0
Pneumonitis * 1	1/187 (0.53%)	1	1/182 (0.55%)	1	1/177 (0.56%)	1
Productive cough * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Pulmonary embolism * 1	2/187 (1.07%)	2	4/182 (2.20%)	4	2/177 (1.13%)	2
Respiratory failure * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis exfoliative generalised * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	1/177 (0.56%)	1
Palmar-plantar erythrodysaesthesia syndrome * 1	0/187 (0.00%)	0	2/182 (1.10%)	2	1/177 (0.56%)	1
Vasculitic ulcer * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Vascular disorders
Deep vein thrombosis * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Embolism * 1	0/187 (0.00%)	0	0/182 (0.00%)	0	3/177 (1.69%)	3
Embolism venous * 1	0/187 (0.00%)	0	1/182 (0.55%)	1	0/177 (0.00%)	0
Hypotension * 1	1/187 (0.53%)	1	0/182 (0.00%)	0	0/177 (0.00%)	0
1 Term from vocabulary, MedDRA v25.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Avelumab		Avelumab + PLD		Pegylated Liposomal Doxorubicin (PLD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	173/187 (92.51%)		176/182 (96.70%)		167/177 (94.35%)
Blood and lymphatic system disorders
Anaemia * 1	32/187 (17.11%)	68	56/182 (30.77%)	131	42/177 (23.73%)	77
Neutropenia * 1	1/187 (0.53%)	2	27/182 (14.84%)	58	25/177 (14.12%)	52
Endocrine disorders
Hypothyroidism * 1	9/187 (4.81%)	11	20/182 (10.99%)	22	2/177 (1.13%)	2
Gastrointestinal disorders
Abdominal distension * 1	14/187 (7.49%)	19	18/182 (9.89%)	21	18/177 (10.17%)	20
Abdominal pain * 1	54/187 (28.88%)	69	47/182 (25.82%)	67	38/177 (21.47%)	48
Abdominal pain upper * 1	10/187 (5.35%)	10	17/182 (9.34%)	22	13/177 (7.34%)	13
Ascites * 1	12/187 (6.42%)	16	5/182 (2.75%)	9	4/177 (2.26%)	7
Constipation * 1	35/187 (18.72%)	47	48/182 (26.37%)	69	46/177 (25.99%)	58
Diarrhoea * 1	42/187 (22.46%)	61	36/182 (19.78%)	57	32/177 (18.08%)	45
Dyspepsia * 1	7/187 (3.74%)	7	18/182 (9.89%)	25	14/177 (7.91%)	15
Gastrooesophageal reflux disease * 1	9/187 (4.81%)	9	9/182 (4.95%)	11	14/177 (7.91%)	17
Nausea * 1	53/187 (28.34%)	66	87/182 (47.80%)	131	76/177 (42.94%)	117
Stomatitis * 1	8/187 (4.28%)	13	53/182 (29.12%)	125	35/177 (19.77%)	73
Vomiting * 1	43/187 (22.99%)	63	43/182 (23.63%)	65	44/177 (24.86%)	58
General disorders
Asthenia * 1	18/187 (9.63%)	27	30/182 (16.48%)	68	14/177 (7.91%)	18
Chills * 1	18/187 (9.63%)	20	14/182 (7.69%)	15	3/177 (1.69%)	3
Fatigue * 1	63/187 (33.69%)	88	77/182 (42.31%)	147	55/177 (31.07%)	78
Influenza like illness * 1	6/187 (3.21%)	7	10/182 (5.49%)	13	1/177 (0.56%)	1
Malaise * 1	5/187 (2.67%)	5	11/182 (6.04%)	14	6/177 (3.39%)	6
Mucosal inflammation * 1	4/187 (2.14%)	7	24/182 (13.19%)	45	19/177 (10.73%)	29
Oedema peripheral * 1	13/187 (6.95%)	16	24/182 (13.19%)	32	14/177 (7.91%)	16
Pyrexia * 1	27/187 (14.44%)	32	36/182 (19.78%)	61	16/177 (9.04%)	20
Infections and infestations
Urinary tract infection * 1	15/187 (8.02%)	22	20/182 (10.99%)	29	12/177 (6.78%)	21
Injury, poisoning and procedural complications
Infusion related reaction * 1	13/187 (6.95%)	17	17/182 (9.34%)	20	14/177 (7.91%)	14
Investigations
Alanine aminotransferase increased * 1	4/187 (2.14%)	8	16/182 (8.79%)	22	2/177 (1.13%)	3
Aspartate aminotransferase increased * 1	4/187 (2.14%)	7	18/182 (9.89%)	30	2/177 (1.13%)	2
Blood alkaline phosphatase increased * 1	4/187 (2.14%)	5	11/182 (6.04%)	20	2/177 (1.13%)	4
Gamma-glutamyltransferase increased * 1	13/187 (6.95%)	16	13/182 (7.14%)	30	6/177 (3.39%)	9
Lymphocyte count decreased * 1	1/187 (0.53%)	1	13/182 (7.14%)	54	4/177 (2.26%)	4
Neutrophil count decreased * 1	4/187 (2.14%)	10	17/182 (9.34%)	84	9/177 (5.08%)	33
Platelet count decreased * 1	5/187 (2.67%)	8	10/182 (5.49%)	22	7/177 (3.95%)	16
Weight decreased * 1	10/187 (5.35%)	11	13/182 (7.14%)	19	13/177 (7.34%)	19
White blood cell count decreased * 1	6/187 (3.21%)	7	15/182 (8.24%)	70	15/177 (8.47%)	41
C-reactive protein increased * 1	0/187 (0.00%)	0	10/182 (5.49%)	13	3/177 (1.69%)	3
Metabolism and nutrition disorders
Decreased appetite * 1	36/187 (19.25%)	41	51/182 (28.02%)	69	37/177 (20.90%)	45
Hypoalbuminaemia * 1	8/187 (4.28%)	16	13/182 (7.14%)	24	6/177 (3.39%)	8
Hypokalaemia * 1	5/187 (2.67%)	12	12/182 (6.59%)	17	11/177 (6.21%)	19
Hypomagnesaemia * 1	10/187 (5.35%)	12	8/182 (4.40%)	15	7/177 (3.95%)	7
Musculoskeletal and connective tissue disorders
Arthralgia * 1	19/187 (10.16%)	22	17/182 (9.34%)	20	10/177 (5.65%)	12
Back pain * 1	22/187 (11.76%)	25	18/182 (9.89%)	28	21/177 (11.86%)	25
Myalgia * 1	9/187 (4.81%)	11	14/182 (7.69%)	21	10/177 (5.65%)	10
Pain in extremity * 1	4/187 (2.14%)	4	18/182 (9.89%)	20	13/177 (7.34%)	14
Nervous system disorders
Dizziness * 1	5/187 (2.67%)	5	17/182 (9.34%)	19	8/177 (4.52%)	8
Headache * 1	15/187 (8.02%)	16	29/182 (15.93%)	34	11/177 (6.21%)	12
Neuropathy peripheral * 1	2/187 (1.07%)	2	10/182 (5.49%)	12	4/177 (2.26%)	4
Psychiatric disorders
Anxiety * 1	7/187 (3.74%)	7	10/182 (5.49%)	11	6/177 (3.39%)	7
Respiratory, thoracic and mediastinal disorders
Cough * 1	17/187 (9.09%)	17	28/182 (15.38%)	45	24/177 (13.56%)	27
Dyspnoea * 1	34/187 (18.18%)	45	32/182 (17.58%)	44	25/177 (14.12%)	32
Oropharyngeal pain * 1	2/187 (1.07%)	2	12/182 (6.59%)	12	8/177 (4.52%)	8
Skin and subcutaneous tissue disorders
Alopecia * 1	3/187 (1.60%)	3	18/182 (9.89%)	18	7/177 (3.95%)	7
Dry skin * 1	5/187 (2.67%)	5	23/182 (12.64%)	25	8/177 (4.52%)	9
Palmar-plantar erythrodysaesthesia syndrome * 1	1/187 (0.53%)	1	61/182 (33.52%)	163	40/177 (22.60%)	74
Pruritus * 1	13/187 (6.95%)	14	21/182 (11.54%)	34	8/177 (4.52%)	9
Rash * 1	12/187 (6.42%)	21	51/182 (28.02%)	126	21/177 (11.86%)	26
Rash maculo-papular * 1	4/187 (2.14%)	5	14/182 (7.69%)	40	11/177 (6.21%)	19
Skin hyperpigmentation * 1	0/187 (0.00%)	0	10/182 (5.49%)	10	10/177 (5.65%)	10
Erythema * 1	4/187 (2.14%)	4	10/182 (5.49%)	15	5/177 (2.82%)	7
1 Term from vocabulary, MedDRA v25.0; * 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):

Pujade-Lauraine E, Fujiwara K, Ledermann JA, Oza AM, Kristeleit R, Ray-Coquard IL, Richardson GE, Sessa C, Yonemori K, Banerjee S, Leary A, Tinker AV, Jung KH, Madry R, Park SY, Anderson CK, Zohren F, Stewart RA, Wei C, Dychter SS, Monk BJ. Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol. 2021 Jul;22(7):1034-1046. doi: 10.1016/S1470-2045(21)00216-3. Epub 2021 Jun 15.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02580058
• Other Study ID Numbers: B9991009; 2015-003091-77 ( EudraCT Number ); JAVELIN OVARIAN 200 ( Other Identifier: Alias Study Number )
• First Submitted: October 16, 2015
• First Posted: October 20, 2015
• Results First Submitted: September 9, 2019
• Results First Posted: November 19, 2019
• Last Update Posted: July 10, 2023