Trial Outcomes & Findings for Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100) (NCT NCT03642132)

Last Updated: 2023-04-06

Results Overview

Progression-free survival (PFS) was defined as the time from randomization to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

79 participants

Primary outcome timeframe

At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by Blinded Independent Central Review (BICR) regardless of initiation of new anti-cancer therapy

Results posted on

2023-04-06

Participant Flow

As of 19 March 2019, the sponsor decided to stop enrollment/randomization in the study. A total of 104 participants were screened and 79 participants completed screening and randomized in the study before study discontinuation. As only 11% projected enrollment was met at the time of enrollment stop, the original study endpoints are no longer applicable and/or feasible; only the Safety, PK and Immunogenicity Analysis were done and these data are included in this report.

Participant milestones

Participant milestones
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
Chemotherapy Period STARTED	32	13	34
Chemotherapy Period COMPLETED	19	8	27
Chemotherapy Period NOT COMPLETED	13	5	7
Maintenance Period STARTED	18	9	23
Maintenance Period COMPLETED	5	1	9
Maintenance Period NOT COMPLETED	13	8	14
Follow-up Period STARTED	19	9	28
Follow-up Period COMPLETED	14	7	24
Follow-up Period NOT COMPLETED	5	2	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
Chemotherapy Period Adverse Event	1	1	0
Chemotherapy Period Physician's decision	4	1	0
Chemotherapy Period Progressive disease	0	0	1
Chemotherapy Period Study terminated by sponsor	0	0	3
Chemotherapy Period Other	1	0	2
Chemotherapy Period Withdrawal by Subject	7	3	1
Maintenance Period Adverse Event	1	2	0
Maintenance Period Non-compliance with study drug	0	0	1
Maintenance Period Physician's decision	2	2	2
Maintenance Period Progressive disease	9	3	6
Maintenance Period Other	0	0	3
Maintenance Period Withdrawal by Subject	1	1	2
Follow-up Period Other	0	0	1
Follow-up Period Withdrawal by Subject	1	2	0
Follow-up Period Study terminated by sponsor	1	0	1
Follow-up Period Lack of Efficacy	1	0	0
Follow-up Period Death	1	0	2
Follow-up Period Adverse Event	1	0	0

Baseline Characteristics

Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib n=32 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib n=13 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab n=34 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.	Total n=79 Participants Total of all reporting groups
Age, Continuous	61.38 years STANDARD_DEVIATION 11.32 • n=5 Participants	58.46 years STANDARD_DEVIATION 12.67 • n=7 Participants	63.29 years STANDARD_DEVIATION 9.83 • n=5 Participants	61.72 years STANDARD_DEVIATION 10.93 • n=4 Participants
Age, Customized < 65 years	21 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants	49 Participants n=4 Participants
Age, Customized 65 =< 75 years	7 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants	20 Participants n=4 Participants
Age, Customized 75 =< 85 years	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	10 Participants n=4 Participants
Age, Customized >= 85 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Customized Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	13 Participants n=7 Participants	34 Participants n=5 Participants	79 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	11 Participants n=7 Participants	27 Participants n=5 Participants	64 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Blank or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	29 Participants n=5 Participants	10 Participants n=7 Participants	24 Participants n=5 Participants	63 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by Blinded Independent Central Review (BICR) regardless of initiation of new anti-cancer therapy

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first dose of study treatment through up to 30 days after minimum last dose of study treatment or start day of new anti-cancer drug therapy minus 1 day (maximum up to 3.5 years approximately)

Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug (avelumab, talazoparib, bevacizumab, carboplatin, paclitaxel). Participants was classified according to the study treatment assigned at randomization unless the incorrect treatment(s) was/were received throughout the dosing period in which case participants would be classified according to the first study treatment received.

An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death, was lifethreatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect or considered to be an important medical event. AEs included SAEs and non-serious AEs. On-treatment period was defined as the time from the first dose of study treatment through up to 30 days after minimum last dose of study treatment or start day of new anti-cancer drug therapy minus 1 day.

Outcome measures

Outcome measures
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib n=29 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib n=13 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab n=34 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
Number of Participants With Treatment-Emergent Adverse Events (On-Treatment Period)	29 Participants	13 Participants	34 Participants

SECONDARY outcome

Timeframe: Day 1 pre-dose of Cycles 1, 2, 3, and 4 in the chemotherapy period and Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period and at the end of treatment/withdrawal, up to 27 months.

Population: The immunogenicity analysis set was a subset of the safety analysis set and included participants in Arm A (Chemotherapy +Avelumab -\> Avelumab + Talazoparib) only, who had at least 1 ADA sample collected. Only avelumab containing arm (Arm A) was included as the analysis was against avelumab.

Predose Anti-drug antibodies (ADA) samples were collected within 2 hours prior to avelumab dosing and drawn from the contralateral arm of the avelumab infusion.

Outcome measures

Outcome measures
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib n=29 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
Number of Participants With ADA Against Avelumab by Never and Ever Positive Status ADA never-positive	17 Participants	—	—
Number of Participants With ADA Against Avelumab by Never and Ever Positive Status ADA ever-positive	12 Participants	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)

Population: The pharmacokinetic (PK) concentration analysis set was a subset of the safety analysis set and included participants who had at least 1 concentration above the below limit of quantitation (BLQ) of either avelumab or talazoparib. Only avelumab containing arm (Arm A) was applicable as it was an analysis of avelumab concentration. Here, "Number of Participants analyzed" signifies number of participants evaluable for this outcome measure.

Ctrough was defined as predose concentration during multiple dosing and it was observed directly from data

Outcome measures

Outcome measures
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib n=29 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Chemotherapy Period) Cycle 1 Day 1 0H	0.000 mcg/mL Interval 0.0 to 5.61	—	—
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Chemotherapy Period) Cycle 2 Day 1 0H	4.370 mcg/mL Interval 0.0 to 10.8	—	—
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Chemotherapy Period) Cycle 3 Day 1 0H	6.100 mcg/mL Interval 0.0 to 20.9	—	—
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Chemotherapy Period) Cycle 4 Day 1 0H	10.00 mcg/mL Interval 0.686 to 16.1	—	—

SECONDARY outcome

Timeframe: Pre-dose on Days 1 and 29 of Cycle 1 and Day 1 of Cycles 2, 4, 6, and 10 in the maintenance period (1 cycle = 6 weeks) and at the end of treatment, up to 27 months.

Ctrough was defined as predose concentration during multiple dosing and it was observed directly from data

Outcome measures

Outcome measures
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib n=29 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period) Cycle 1 Day 1 0H	3.470 mcg/mL Interval 0.0 to 25.7	—	—
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period) Cycle 1 Day 29 0H	41.60 mcg/mL Interval 19.5 to 78.0	—	—
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period) Cycle 2 Day 1 0H	33.90 mcg/mL Interval 25.7 to 63.6	—	—
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period) Cycle 4 Day 1 0H	28.60 mcg/mL Interval 23.3 to 41.0	—	—
Pre-dose/Trough Concentration (Ctrough) for Avelumab (Maintenance Period) Cycle 6 Day 1 0H	20.6 mcg/mL Interval 20.6 to 20.6	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycles 1, 2, 3, and 4 in the chemotherapy period (1 cycle = 3 weeks)

Cmax was defined as maximum observed plasma concentration and it was observed directly from data

Outcome measures

Outcome measures
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib n=29 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
Cmax for Avelumab (Chemotherapy Period) Cycle 1 Day 1 1H/End of infusion(EOI)	218.0 mcg/mL Interval 132.0 to 318.0	—	—
Cmax for Avelumab (Chemotherapy Period) Cycle 2 Day 1 1H/End of infusion(EOI)	222.5 mcg/mL Interval 29.8 to 319.0	—	—
Cmax for Avelumab (Chemotherapy Period) Cycle 3 Day 1 1H/End of infusion(EOI)	253.0 mcg/mL Interval 157.0 to 349.0	—	—
Cmax for Avelumab (Chemotherapy Period) Cycle 4 Day 1 1H/End of infusion(EOI)	243.0 mcg/mL Interval 139.0 to 343.0	—	—

SECONDARY outcome

Cmax was defined as maximum observed plasma concentration and it was observed directly from data

Outcome measures

Outcome measures
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib n=29 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
Cmax for Avelumab (Maintenance Period) Cycle 1 Day 1 1H/End of infusion(EOI)	227.0 mcg/mL Interval 154.0 to 282.0	—	—
Cmax for Avelumab (Maintenance Period) Cycle 1 Day 29 1H/End of infusion(EOI)	279.0 mcg/mL Interval 190.0 to 485.0	—	—
Cmax for Avelumab (Maintenance Period) Cycle 2 Day 1 1H/End of infusion(EOI)	222.0 mcg/mL Interval 158.0 to 289.0	—	—
Cmax for Avelumab (Maintenance Period) Cycle 4 Day 1 1H/End of infusion(EOI)	225.0 mcg/mL Interval 224.0 to 226.0	—	—
Cmax for Avelumab (Maintenance Period) Cycle 6 Day 1 1H/End of infusion(EOI)	219.0 mcg/mL Interval 219.0 to 219.0	—	—

SECONDARY outcome

Timeframe: Pre-dose on Days 1, 15 and 29 of Cycle 1

Population: The pharmacokinetic (PK) concentration analysis set was a subset of the safety analysis set and included participants who had at least 1 concentration above the lower limit of quantitation (LLQ) of either avelumab or talazoparib. Only the talazoprib containing arms (Arm A and Arm B) were applicable as it was an analysis of talazoprib concentration. It is anticipated the number of participants for PK concentration analysis set would be different from safety analysis set.

Ctrough was defined as predose concentration during multiple dosing and it was observed directly from data.

Outcome measures

Outcome measures
Measure	Chemotherapy +Avelumab -> Avelumab + Talazoparib n=9 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 intravenously(IV) over 3 hours followed by carboplatin area under the concentration (AUC) 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles along with avelumab 800 mg administered IV on Day 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received avelumab 800 mg administered IV on Days 1, 15 and 29 of each 6-week cycle in combination with talazoparib 0.75 mg self-administered orally once per day. A cycle was defined as 3 weeks (21 days) in the chemotherapy period and 6 weeks (42 days) in the maintenance period, respectively.	Chemotherapy -> Talazoparib n=8 Participants In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Days 1 of each 3-week cycle for 6 cycles. In maintenance period, participants received talazoparib 0.75 mg self-administered orally once a day, every day of each 6-week cycle.	Chemotherapy + Bevacizumab -> Bevacizumab In chemotherapy period, participants received paclitaxel 175 mg/m\^2 IV over 3 hours followed by carboplatin AUC 5 or 6 IV over 15-60 minutes on Day 1 of each 3-week cycle for 6 cycles along with bevacizumab 15 mg/kg IV on Day 1 of each 3-week cycle beginning with Cycle 2 for adjuvant participants, and for neoadjuvant participants, bevacizumab was given on Day 1 of each 3-week cycle for Cycles 1, 2, 5, and 6. In maintenance period, participants received bevacizumab 15 mg/kg administered IV on Days 1 and 22 of each 6-week cycle.
Ctrough for Talazoprib (Maintenance Period) Cycle 1 Day 1	0.000 pg/mL Interval 0.0 to 0.0	0.000 pg/mL Interval 0.0 to 0.0	—
Ctrough for Talazoprib (Maintenance Period) Cycle 1 Day 15	2425 pg/mL Interval 1920.0 to 2930.0	1343 pg/mL Interval 865.0 to 1820.0	—
Ctrough for Talazoprib (Maintenance Period) Cycle 1 Day 29	2500 pg/mL Interval 2060.0 to 6470.0	1950 pg/mL Interval 660.0 to 3290.0	—

SECONDARY outcome

Timeframe: From 9 weeks up to approximately 3.5 years

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

OS was defined as the time from the date of randomization to the date of death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At screening, 9 and 18 weeks after date of randomization, then every 12 weeks thereafter until PD by BICR regardless of initiation of new anti-cancer therapy, up to approximately 3.5 years.

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

PFS was defined as the time from the date of randomization to the date of the first documentation of PD or death due to any cause, whichever occured first.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

PFS was defined as the time from randomization to the date of the first documentation of objective progressive disease(PD) or death due to any cause, whichever occured first. Participants was defined as having defective DDR (DDR+) or having intact DDR (DDR ) using a next generation sequencing based assay method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From screening until the participant had objective PD on or prior to start of next-line anti-cancer treatment, and started a second subsequent anti-cancer treatment or the participant died, up to approximately 3.5 years.

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

Progression-free survival on next-line therapy (PFS2) was defined as time from the date of randomization to the start of second subsequent treatment after first documentation of PD, or death from any cause, whichever occured first. Participants was defined as having defective DDR (DDR+) or having intact DDR (DDR ) using a next generation sequencing based assay method

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From screening until death, end of study, or participant withdrawal of consent, whichever occurred first, up to approximately 3.5 years.

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

PFS based on investigator assessment per Gynecological Cancer Intergroup criteria (GCIG) would be assessed incorporating both Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and CA 125. Participants was defined as having defective DDR (DDR+) or having intact DDR (DDR ) using a next generation sequencing based assay method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 years

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

NFOSI-18 was an ovarian cancer-specific symptom index comprised of symptoms rated as highest priority by both oncology clinical experts and women with advanced ovarian cancer. It was specifically designed to be a stand-alone instrument to measure disease-related symptoms, treatment side effects and function/well-being in participants with ovarian cancer. The NFOSI-18 has several subscales: disease-related symptoms physical subscale(9 items), disease-related symptoms emotional subscale(1 item), treatment-related side effect subscale (5 items) and functional well-being (3 items). A high score was good. A score of "0" was a severely symptomatic participant and the highest possible score was an asymptomatic participant.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

The number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest that were defined by tumor cell morphology and the presence or absence of inflammatory cells

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

Determination/estimation of the frequency of mutations (total and non-synonymous) present in baseline tumor derived nucleic acid samples and in baseline circulating tumor DNA.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 years

Population: This OM measure was planned but due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

The EuroQol EQ-5D-5L was a 6 item participant-completed questionnaire designed to assess health status in terms of a single index value or utility score. There are 2 components to the EQ-5D-5L, a Health State Profile which had individuals rate their level of problems (none, slight, moderate, severe, extreme/unable) in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and a Visual Analogue Scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). Published weights were available that allow for imputation of the index score. Overall index scores ranged from 0 to 1, with low scores representing a higher level of dysfunction.

Outcome measures

Outcome data not reported

Adverse Events

Chemotherapy +Avelumab -> Avelumab + Talazoparib

Serious events: 9 serious events

Other events: 29 other events

Deaths: 1 deaths

Chemotherapy -> Talazoparib

Serious events: 4 serious events

Other events: 13 other events

Deaths: 0 deaths

Chemotherapy + Bevacizumab -> Bevacizumab

Serious events: 15 serious events

Other events: 34 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

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