Trial Outcomes & Findings for 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) (NCT NCT02580058)

Last Updated: 2023-07-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

566 participants

Primary outcome timeframe

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).

Results posted on

2023-07-10

Participant Flow

Data reported based on last participant last visit (LPLV) date (12 July 2022).

Participant milestones

Participant milestones
Measure	Avelumab Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD 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.	Pegylated Liposomal Doxorubicin (PLD) PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Study STARTED	188	188	190
Overall Study Treated	187	182	177
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	188	188	190

Reasons for withdrawal

Reasons for withdrawal
Measure	Avelumab Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD 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.	Pegylated Liposomal Doxorubicin (PLD) PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Study Adverse Event	16	30	20
Overall Study Death	4	4	5
Overall Study Physician Decision	1	3	11
Overall Study Other	5	1	3
Overall Study Withdrawal by Subject	4	7	31
Overall Study Global Deterioration of Health Status	19	18	24
Overall Study No Longer Meets Eligibility Criteria	1	0	2
Overall Study Progressive Disease	137	125	94
Overall Study Non-Compliance With Study Drug	1	0	0

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Avelumab n=188 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=188 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=190 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.	Total n=566 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	111 Participants n=93 Participants	124 Participants n=4 Participants	114 Participants n=27 Participants	349 Participants n=483 Participants
Age, Categorical >=65 years	77 Participants n=93 Participants	64 Participants n=4 Participants	76 Participants n=27 Participants	217 Participants n=483 Participants
Age, Continuous	61.0 years STANDARD_DEVIATION 10.26 • n=93 Participants	59.5 years STANDARD_DEVIATION 10.05 • n=4 Participants	60.4 years STANDARD_DEVIATION 10.64 • n=27 Participants	60.3 years STANDARD_DEVIATION 10.32 • n=483 Participants
Sex: Female, Male Female	188 Participants n=93 Participants	188 Participants n=4 Participants	190 Participants n=27 Participants	566 Participants n=483 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	3 Participants n=4 Participants	1 Participants n=27 Participants	6 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	176 Participants n=93 Participants	176 Participants n=4 Participants	183 Participants n=27 Participants	535 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=93 Participants	9 Participants n=4 Participants	6 Participants n=27 Participants	25 Participants n=483 Participants
Race/Ethnicity, Customized Race · Black or African American	2 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants	10 Participants n=483 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Race · Asian	34 Participants n=93 Participants	53 Participants n=4 Participants	46 Participants n=27 Participants	133 Participants n=483 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Race · White	148 Participants n=93 Participants	133 Participants n=4 Participants	135 Participants n=27 Participants	416 Participants n=483 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants
Race/Ethnicity, Customized Race · Unknown	2 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants

PRIMARY outcome

Timeframe: 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).

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

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.

Outcome measures

Outcome measures
Measure	Avelumab n=188 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=188 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=190 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Overall Survival (OS)	11.8 months Interval 8.9 to 14.1	15.7 months Interval 12.7 to 18.7	13.1 months Interval 11.8 to 15.5

PRIMARY outcome

Timeframe: 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.

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

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.

Outcome measures

Outcome measures
Measure	Avelumab n=188 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=188 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=190 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Progression Free Survival (PFS) Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	1.9 months Interval 1.8 to 1.9	3.7 months Interval 3.3 to 5.1	3.5 months Interval 2.1 to 4.0

SECONDARY outcome

Timeframe: 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.

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

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.

Outcome measures

Outcome measures
Measure	Avelumab n=188 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=188 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=190 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Objective Response Rate (ORR) Based on BICR Assessment	3.7 percentage of participants Interval 1.5 to 7.5	13.3 percentage of participants Interval 8.8 to 19.0	4.2 percentage of participants Interval 1.8 to 8.1

SECONDARY outcome

Timeframe: 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.

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

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.

Outcome measures

Outcome measures
Measure	Avelumab n=188 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=188 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=190 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
ORR Based on Investigator Assessment	5.3 percentage of participants Interval 2.6 to 9.6	18.6 percentage of participants Interval 13.3 to 24.9	9.5 percentage of participants Interval 5.7 to 14.6

SECONDARY outcome

Timeframe: 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.

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

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.

Outcome measures

Outcome measures
Measure	Avelumab n=188 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=188 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=190 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
PFS Based on Investigator Assessment According to RECIST Version 1.1	1.9 month Interval 1.8 to 1.9	4.7 month Interval 3.7 to 6.0	3.7 month Interval 3.5 to 5.4

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=7 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=25 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=8 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Duration of Response (DR) Based on BICR Assessment	9.2 months Interval 6.4 to The upper limit of 95% confidence interval (CI) was not estimable due to the small number of events.	8.5 months Interval 6.1 to The upper limit of 95% CI was not estimable due to the small number of events.	13.1 months Interval 5.5 to The upper limit of 95% CI was not estimable due to the small number of events.

SECONDARY outcome

Timeframe: 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 measures

Outcome measures
Measure	Avelumab n=10 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=35 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=18 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
DR Based on Investigator Assessment	10.4 months Interval 3.7 to The upper limit of 95% CI was not estimable due to the small number of events.	7.6 months Interval 5.6 to 9.1	7.4 months Interval 3.6 to 11.2

SECONDARY outcome

Timeframe: 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.

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

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.

Outcome measures

Outcome measures
Measure	Avelumab n=188 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=188 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=190 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Disease Control (DC) Rate Based on BICR Assessment	33.0 percentage of participants Interval 26.3 to 40.2	57.4 percentage of participants Interval 50.0 to 64.6	48.9 percentage of participants Interval 41.6 to 56.3

SECONDARY outcome

Timeframe: 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.

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

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.

Outcome measures

Outcome measures
Measure	Avelumab n=188 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=188 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=190 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
DC Rate Based on Investigator Assessment	34.0 percentage of participants Interval 27.3 to 41.3	61.7 percentage of participants Interval 54.3 to 68.7	54.7 percentage of participants Interval 47.4 to 62.0

SECONDARY outcome

Timeframe: 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.

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

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.

Outcome measures

Outcome measures
Measure	Avelumab n=187 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=182 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=177 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAE	180 Participants	180 Participants	173 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Treatment emergent SAEs	72 Participants	74 Participants	51 Participants

SECONDARY outcome

Timeframe: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Population: '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.

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).

Outcome measures

Outcome measures
Measure	Avelumab n=187 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=182 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=177 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With Laboratory Abnormalities Platelet count decreased	33 Participants	48 Participants	50 Participants
Number of Participants With Laboratory Abnormalities Anemia	135 Participants	155 Participants	144 Participants
Number of Participants With Laboratory Abnormalities Lymphocyte count decreased	89 Participants	148 Participants	107 Participants
Number of Participants With Laboratory Abnormalities Neutrophil count decreased	26 Participants	80 Participants	62 Participants
Number of Participants With Laboratory Abnormalities Creatinine increased	154 Participants	151 Participants	120 Participants
Number of Participants With Laboratory Abnormalities Serum amylase increased	43 Participants	35 Participants	27 Participants
Number of Participants With Laboratory Abnormalities Lipase increased	27 Participants	33 Participants	21 Participants

SECONDARY outcome

Timeframe: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Population: '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.

Vital signs included blood pressure and pulse rate. Changes from baseline in sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were summarized.

Outcome measures

Outcome measures
Measure	Avelumab n=187 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=182 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=177 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Change From Baseline in Vital Signs - Blood Pressure DBP Cycle 2 Day 15	0.1 mm Hg Standard Deviation 10.05	-2.8 mm Hg Standard Deviation 9.19	-0.1 mm Hg Standard Deviation 8.83
Change From Baseline in Vital Signs - Blood Pressure DBP Cycle 3 Day 1	0 mm Hg Standard Deviation 10.81	-2.7 mm Hg Standard Deviation 8.95	-0.2 mm Hg Standard Deviation 8.96
Change From Baseline in Vital Signs - Blood Pressure SBP Cycle 2 Day 15	-0.6 mm Hg Standard Deviation 14.11	-3.7 mm Hg Standard Deviation 14.78	-1.8 mm Hg Standard Deviation 14.98
Change From Baseline in Vital Signs - Blood Pressure SBP Cycle 3 Day 15	-0.2 mm Hg Standard Deviation 13.78	-2.1 mm Hg Standard Deviation 15.30	-2.2 mm Hg Standard Deviation 13.96
Change From Baseline in Vital Signs - Blood Pressure SBP End of Treatment	-0.9 mm Hg Standard Deviation 17.21	-1.0 mm Hg Standard Deviation 16.83	-3.2 mm Hg Standard Deviation 15.92
Change From Baseline in Vital Signs - Blood Pressure DBP Cycle 1 Day 15	0.1 mm Hg Standard Deviation 9.79	-2.2 mm Hg Standard Deviation 9.12	0.7 mm Hg Standard Deviation 8.89
Change From Baseline in Vital Signs - Blood Pressure DBP Cycle 2 Day 1	-1.1 mm Hg Standard Deviation 9.61	-2.8 mm Hg Standard Deviation 8.01	-0.1 mm Hg Standard Deviation 9.34
Change From Baseline in Vital Signs - Blood Pressure DBP Cycle 3 Day 15	-0.6 mm Hg Standard Deviation 9.25	-2.3 mm Hg Standard Deviation 8.56	-0.5 mm Hg Standard Deviation 8.67
Change From Baseline in Vital Signs - Blood Pressure DBP End of Treatment	1.1 mm Hg Standard Deviation 10.87	-0.3 mm Hg Standard Deviation 11.08	0.8 mm Hg Standard Deviation 10.40
Change From Baseline in Vital Signs - Blood Pressure SBP Cycle 1 Day 15	-0.9 mm Hg Standard Deviation 14.35	-2.3 mm Hg Standard Deviation 13.12	-1.0 mm Hg Standard Deviation 13.94
Change From Baseline in Vital Signs - Blood Pressure SBP Cycle 2 Day 1	-2.2 mm Hg Standard Deviation 14.44	-3.4 mm Hg Standard Deviation 13.70	-2.8 mm Hg Standard Deviation 13.39
Change From Baseline in Vital Signs - Blood Pressure SBP Cycle 3 Day 1	-0.2 mm Hg Standard Deviation 15.59	-2.7 mm Hg Standard Deviation 14.36	-1.5 mm Hg Standard Deviation 14.14

SECONDARY outcome

Timeframe: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Population: '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.

Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized.

Outcome measures

Outcome measures
Measure	Avelumab n=187 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=182 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=177 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Change From Baseline in Vital Signs - Pulse Rate Cycle 3 Day 1	2.4 bpm Standard Deviation 10.00	2.1 bpm Standard Deviation 11.78	1.4 bpm Standard Deviation 11.14
Change From Baseline in Vital Signs - Pulse Rate Cycle 3 Day 15	3.0 bpm Standard Deviation 12.23	1.4 bpm Standard Deviation 11.44	2.4 bpm Standard Deviation 10.41
Change From Baseline in Vital Signs - Pulse Rate Cycle 1 Day 15	2.9 bpm Standard Deviation 9.95	1.8 bpm Standard Deviation 12.10	3.5 bpm Standard Deviation 10.70
Change From Baseline in Vital Signs - Pulse Rate Cycle 2 Day 1	2.6 bpm Standard Deviation 10.92	2.9 bpm Standard Deviation 11.18	1.7 bpm Standard Deviation 9.71
Change From Baseline in Vital Signs - Pulse Rate Cycle 2 Day 15	2.9 bpm Standard Deviation 11.19	3.5 bpm Standard Deviation 11.79	3.2 bpm Standard Deviation 11.54
Change From Baseline in Vital Signs - Pulse Rate End of Treatment	7.7 bpm Standard Deviation 14.27	7.4 bpm Standard Deviation 13.70	5.7 bpm Standard Deviation 14.10

SECONDARY outcome

Timeframe: From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Population: '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.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=187 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=182 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=177 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With Electrocardiogram (ECG) Abnormalities QT >500 ms	1 Participants	1 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF increase from baseline >30 ms	19 Participants	24 Participants	13 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF >450 ms	18 Participants	27 Participants	14 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF >480 ms	4 Participants	8 Participants	5 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcP increase from baseline >60 ms	6 Participants	5 Participants	4 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities PR >=220 ms and increase from baseline >=20 ms	3 Participants	4 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QRS >=120 ms	7 Participants	9 Participants	9 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT increase from baseline >30 ms	26 Participants	40 Participants	47 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT increase from baseline >60 ms	5 Participants	9 Participants	4 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT >450 ms	6 Participants	10 Participants	5 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QT >480 ms	1 Participants	2 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB increase from baseline >30 ms	33 Participants	36 Participants	22 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB increase from baseline >60 ms	9 Participants	7 Participants	8 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB >450 ms	56 Participants	63 Participants	45 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB >480 ms	9 Participants	19 Participants	9 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcB >500 ms	5 Participants	9 Participants	5 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF increase from baseline >60 ms	6 Participants	5 Participants	5 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcF >500 ms	3 Participants	2 Participants	4 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcP increase from baseline >30 ms	17 Participants	23 Participants	12 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcP >450 ms	19 Participants	29 Participants	17 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcP >480 ms	2 Participants	7 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities QTcP >500 ms	1 Participants	2 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Heart rate <=50 bpm and decrease >= 20 bpm	0 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Abnormalities Heart rate >=120 bpm and increase >= 20 bpm	5 Participants	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Screening, Cycle 3 Day 1 (repeated every 2 cycles) to the end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.

Population: '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.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=129 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=154 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=132 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With % Left Ventricular Ejection Fraction (LVEF) Decrease From Baseline >= 10 point decrease from baseline	8 Participants	22 Participants	13 Participants
Number of Participants With % Left Ventricular Ejection Fraction (LVEF) Decrease From Baseline >= 15 point decrease from baseline	3 Participants	8 Participants	3 Participants

SECONDARY outcome

Timeframe: Biomarkers are measured only at screening.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=170 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=173 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=165 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With PD-L1 Expression for PFS (Based on BICR Assessment) and for OS	100 Participants	100 Participants	88 Participants

SECONDARY outcome

Timeframe: Biomarkers are measured only at screening.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=165 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=171 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=164 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With CD8 Expression for PFS (Based on BICR Assessment) and for OS	76 Participants	80 Participants	72 Participants

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=152 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=166 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=148 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With Improved, Stable and Deterioration Based on 10-Point Change for EORTC QLQ-C30 Global QoL Improved	23 Participants	20 Participants	26 Participants
Number of Participants With Improved, Stable and Deterioration Based on 10-Point Change for EORTC QLQ-C30 Global QoL Deterioration	46 Participants	65 Participants	46 Participants
Number of Participants With Improved, Stable and Deterioration Based on 10-Point Change for EORTC QLQ-C30 Global QoL Stable	83 Participants	81 Participants	76 Participants

SECONDARY outcome

Timeframe: From Day 1 of Cycle 1 to prior to end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.

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

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.

Outcome measures

Outcome measures
Measure	Avelumab n=188 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=188 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=190 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Time to Deterioration in Abdominal/GI Symptom Subscale of EORTC QLQ-OV28	NA months The median estimates of time to event, upper and lower limits of 95% CI were not estimable due to the small number of events.	11.1 months Interval 6.5 to The upper limit of 95% CI was not estimable due to the small number of events.	10.6 months Interval 9.2 to The upper limit of 95% CI was not estimable due to the small number of events.

SECONDARY outcome

Timeframe: Baseline and end of treatment/withdrawal visit

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=111 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=116 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=111 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Change From Baseline in EQ-VAS Score at End of Treatment	-13.6 scores on a scale Standard Deviation 20.56	-11.2 scores on a scale Standard Deviation 19.79	-7.7 scores on a scale Standard Deviation 22.26

SECONDARY outcome

Timeframe: At predose (0 H) on Cycle 2 Day 1

Population: 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.

Ctrough was defined as predose concentration during multiple dosing, and can be observed directly from data.

Outcome measures

Outcome measures
Measure	Avelumab n=136 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=139 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Serum Trough Concentration (Ctrough) For Avelumab Following Cycle 2 Day 1 Pegylated Liposomal Doxorubicin (PLD) Dose	21.1 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 89	23.19 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 74	—

SECONDARY outcome

Timeframe: At postdose (end of infusion, 1H) on Cycle 2 Day 1

Population: 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.

Cmax was defined as maximum observed serum concentration, and can be observed directly from data.

Outcome measures

Outcome measures
Measure	Avelumab n=104 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=110 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Serum Maximum Concentration (Cmax) For Avelumab Following Cycle 2 Day 1 PLD Dose	231.6 mcg/mL Geometric Coefficient of Variation 43	207.9 mcg/mL Geometric Coefficient of Variation 71	—

SECONDARY outcome

Timeframe: From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose

Population: 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.

Cmax was defined as maximum observed serum concentration, and can be observed directly from data.

Outcome measures

Outcome measures
Measure	Avelumab n=15 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=15 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Cmax For Doxorubicin Following Cycle 2 Day 1 PLD Dose	26810 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 14	25850 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 17	—

SECONDARY outcome

Timeframe: From 0 through 24 hours postdose

Population: 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.

AUC24 was defined as area under the concentration time profile from time zero to 24 hours.

Outcome measures

Outcome measures
Measure	Avelumab n=14 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=14 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Area Under The Concentration Time Profile From Time Zero to 24 Hours (AUC24) For Doxorubicin Following Cycle 2 Day 1 PLD Dose	567600 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 11	541700 nanogramhour per milliliter (nghr/mL) Geometric Coefficient of Variation 14	—

SECONDARY outcome

Timeframe: From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose

Population: 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.

AUC336 was defined as area under the concentration time profile from time zero to 336 hours.

Outcome measures

Outcome measures
Measure	Avelumab n=13 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=12 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Area Under The Concentration Time Profile From Time Zero to 336 Hours (AUC336) For Doxorubicin Following Cycle 2 Day 1 PLD Dose	2848000 ng*hr/mL Geometric Coefficient of Variation 20	2571000 ng*hr/mL Geometric Coefficient of Variation 30	—

SECONDARY outcome

Timeframe: From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose

Population: 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.

AUClast was defined as area under the concentration time profile from time zero to the time of the last quantifiable concentration (Clast).

Outcome measures

Outcome measures
Measure	Avelumab n=15 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=15 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Area Under The Concentration Time Profile From Time Zero to The Last Quantifiable Concentration (AUClast) For Doxorubicin Following Cycle 2 Day 1 PLD Dose	2043000 ng*hr/mL Geometric Coefficient of Variation 119	2052000 ng*hr/mL Geometric Coefficient of Variation 71	—

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=165 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=167 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=332 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With Treatment-Boosted Anti-Drug Antibody (ADA)	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=169 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=167 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=336 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With Treatment-Induced ADA	27 Participants	2 Participants	29 Participants

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Avelumab n=173 Participants Avelumab 10 milligram (mg)/kilogram (kg) given as a 1-hour intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles.	Avelumab + PLD n=169 Participants 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.	Pegylated Liposomal Doxorubicin (PLD) n=342 Participants PLD 40 mg/square meter given as a 1-hour IV infusion Q4W in 4-week cycles.
Number of Participants With Treatment-Induced Neutralizing Antibody (nAb)	5 Participants	1 Participants	6 Participants

Adverse Events

Avelumab

Serious events: 72 serious events

Other events: 173 other events

Deaths: 122 deaths

Avelumab + PLD

Serious events: 74 serious events

Other events: 176 other events

Deaths: 107 deaths

Pegylated Liposomal Doxorubicin (PLD)

Serious events: 51 serious events

Other events: 167 other events

Deaths: 116 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER