Trial Outcomes & Findings for Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer (NCT NCT02657889)

Last Updated: 2022-12-01

Results Overview

DLTs are defined as: Any treatment-related Grade \>=3 non-hematologic clinical (non-laboratory) adverse event (AE); Any treatment-related Grade 3 or Grade 4 non-hematologic laboratory (lab) abnormality if Medical intervention is required to treat the participant or the abnormality leads to hospitalization or the abnormality persists for \>=7 days; Any treatment-related hematologic toxicity specifically defined as: Thrombocytopenia Grade 4 for \>=7 days, or Grade 3 or 4 associated with bleeding or requiring platelet transfusion, Neutropenia Grade 4 for \>=7 days, or Grade 3 or 4 associated with infection or febrile neutropenia, Anemia Grade 4, or Grade 3 or 4 requiring blood transfusion; Any treatment-related AE leading to niraparib dose interruption per the following criteria: A dose interruption for a non-DLT lab abnormality lasting \>=14 days, A dose in interruption per dose modification rules for non-hematologic AE leading to \<80 percent (%) of an intended dose being administered.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

122 participants

Primary outcome timeframe

During Cycle 1, ie, during the first 21 days of treatment

Results posted on

2022-12-01

Participant Flow

This was a multicenter study conducted in the United States.

A total of 122 participants (14 in Phase 1 and 108 in Phase 2) were enrolled in the study (Safety analysis set included all participants who received any amount of study treatment in Phase 1 or Phase 2).

Participant milestones

Participant milestones
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.	Phase 2 OC: Niraparib 200mg + Pembrolizumab Participants with Ovarian Cancer (OC) received recommended phase 2 dose (RP2D) of Niraparib 200 mg orally once daily and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.	Phase 2 TNBC: Niraparib 200mg + Pembrolizumab Participants with Triple Negative Breast Cancer (TNBC) received RP2D of Niraparib 200 mg orally once daily and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: (Up to a Maximum of 22 Months) STARTED	7	7	0	0
Phase 1: (Up to a Maximum of 22 Months) COMPLETED	0	0	0	0
Phase 1: (Up to a Maximum of 22 Months) NOT COMPLETED	7	7	0	0
Phase 2: (Up to a Maximum of 54 Months) STARTED	0	0	53	55
Phase 2: (Up to a Maximum of 54 Months) COMPLETED	0	0	0	0
Phase 2: (Up to a Maximum of 54 Months) NOT COMPLETED	0	0	53	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.	Phase 2 OC: Niraparib 200mg + Pembrolizumab Participants with Ovarian Cancer (OC) received recommended phase 2 dose (RP2D) of Niraparib 200 mg orally once daily and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.	Phase 2 TNBC: Niraparib 200mg + Pembrolizumab Participants with Triple Negative Breast Cancer (TNBC) received RP2D of Niraparib 200 mg orally once daily and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: (Up to a Maximum of 22 Months) Death	5	5	0	0
Phase 1: (Up to a Maximum of 22 Months) Lost to Follow-up	2	0	0	0
Phase 1: (Up to a Maximum of 22 Months) Sponsor decision	0	1	0	0
Phase 1: (Up to a Maximum of 22 Months) Radiologic Disease Progression	0	1	0	0
Phase 2: (Up to a Maximum of 54 Months) Death	0	0	30	42
Phase 2: (Up to a Maximum of 54 Months) Lost to Follow-up	0	0	5	2
Phase 2: (Up to a Maximum of 54 Months) Withdrawal by Subject	0	0	8	2
Phase 2: (Up to a Maximum of 54 Months) Sponsor decision	0	0	2	2
Phase 2: (Up to a Maximum of 54 Months) Radiologic Disease Progression	0	0	6	1
Phase 2: (Up to a Maximum of 54 Months) Physician Decision	0	0	0	1
Phase 2: (Up to a Maximum of 54 Months) Participant request	0	0	2	1
Phase 2: (Up to a Maximum of 54 Months) Participants went on Rollover Study	0	0	0	4

Baseline Characteristics

Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=7 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=7 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.	Phase 2 OC: Niraparib 200mg + Pembrolizumab n=53 Participants Participants with Ovarian Cancer (OC) received recommended phase 2 dose (RP2D) of Niraparib 200 mg orally once daily and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.	Phase 2 TNBC: Niraparib 200mg + Pembrolizumab n=55 Participants Participants with Triple Negative Breast Cancer (TNBC) received RP2D of Niraparib 200 mg orally once daily and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.	Total n=122 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	37 Participants n=5 Participants	47 Participants n=4 Participants	92 Participants n=21 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants	8 Participants n=4 Participants	30 Participants n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	53 Participants n=5 Participants	55 Participants n=4 Participants	122 Participants n=21 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	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	7 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	50 Participants n=5 Participants	51 Participants n=4 Participants	113 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) 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	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants	9 Participants n=21 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	7 Participants n=7 Participants	46 Participants n=5 Participants	43 Participants n=4 Participants	103 Participants n=21 Participants
Race (NIH/OMB) More than one race	NA Participants n=5 Participants	NA Participants n=7 Participants	NA Participants n=5 Participants	NA Participants n=4 Participants	NA Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Region of Enrollment United States	7 Participants n=5 Participants	7 Participants n=7 Participants	53 Participants n=5 Participants	55 Participants n=4 Participants	122 Participants n=21 Participants

PRIMARY outcome

Timeframe: During Cycle 1, ie, during the first 21 days of treatment

Population: DLT Analysis Set comprised of all Phase 1 participants who completed the first cycle of therapy. The assessment of DLTs in Phase 1 included only those participants completing the first cycle of therapy, unless the participant discontinued study drug due to a DLT. Only those participants with data available at specified data point were analyzed.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=6 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=6 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Number of Participants Reporting Dose-Limiting Toxicities (DLTs)	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 40 weeks

Population: Full Analysis Set comprised of all Phase 2 participants who received any amount of study treatment. Only those participants with data available at specified time points were analyzed. .

ORR is defined as the percentage of participants with a confirmed best overall response of Complete Response (CR) or Partial Response (PR), RECIST v1.1 for target lesions as assessed by the Investigator. CR is defined as disappearance of all target lesions, Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis; PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the Baseline sum diameters.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=53 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=55 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 2: Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1	15.1 Percentage of participants Interval 7.7 to 25.6	18.2 Percentage of participants Interval 10.2 to 28.9

SECONDARY outcome

Timeframe: Up to a maximum of 22 months

Population: Safety Analysis Set comprised of all participants who received any amount of study treatment in Phase 1 or Phase 2. Only those participants with data available at specified time points were analyzed.

An adverse event was any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. TEAEs were any new AE that begins, or any pre-existing condition that worsens in severity, after at least 1 dose of study treatment has been administered.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=7 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=7 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	7 Participants	7 Participants

SECONDARY outcome

Timeframe: Up to a maximum of 54 months

Population: Safety Analysis Set. Only those participants with data available at specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=53 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=55 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 2: Number of Participants With TEAEs	53 Participants	54 Participants

SECONDARY outcome

Timeframe: Up to a maximum of 54 months

Population: Full Analysis Set. IrRECIST data were invalid due to errors in the collection approach. Hence, data for this outcome measure were not reported. This decision was documented in the final Statistical Analysis Plan (SAP) (Version 2, 21-March-2019) and approved before database lock which occurred on 22-October-2021.

ORR by irRECIST is defined as the percentage of participants with a confirmed best overall response of CR or PR using irRECIST. Immune related complete response (irCR) is defined as at least two radiographic determinations of CR, at least 4 weeks apart and before Immune related progressive disease (irPD - defined as at least two consecutive radiographic determinations of progressive disease \[PD\] at least 4 weeks apart) at least 4 weeks apart. Immune related partial response (irPR) defined as at least two radiographic determinations of PR or better at least 4 weeks apart and before irPD (and not qualifying for an irCR).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to a maximum of 54 months

Population: Full Analysis Set. Only those participants with data available at specified time point were analyzed.

DoR per RECIST v1.1 was defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1 based upon investigator assessment or death due to any cause, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the Baseline sum diameters.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=8 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=10 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 2: Duration of Response (DOR) as Measured by RECIST v1.1	14.4 Months Interval 8.3 to 18.7	21.5 Months Interval 8.4 to \<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.

SECONDARY outcome

Timeframe: Up to a maximum of 54 months

DOR was defined as the time from the initial response (irCR, irPR or irSD) to progression or death, whichever occurs first. Response was to be assessed using the irRECIST. Immune related complete response (irCR) is at least two radiographic determinations of CR at least 4 weeks apart and before Immune related progressive disease (irPD - defined as at least two consecutive radiographic determinations of PD at least 4 weeks apart) at least 4 weeks apart. Immune related partial response (irPR) defined as at least two radiographic determinations of PR or better at least 4 weeks apart and before irPD (and not qualifying for an irCR).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 40 weeks

Population: Full Analysis Set. Only those participants with data available at specified time points were analyzed.

DCR is defined as the percentage of participants who achieved a CR or PR or stable disease (SD) using RECIST (v1.1) as assessed by the investigator.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=53 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=55 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 2: Disease Control Rate (DCR) as Measured by RECIST v1.1	58.5 Percentage of participants Interval 46.3 to 70.0	41.8 Percentage of participants Interval 30.5 to 53.8

SECONDARY outcome

Timeframe: Up to a maximum of 54 months

DCR is percentage of participants achieving best overall response of confirmed irCR, irPR, or immune-related stable disease (irSD) (lasting at least 5 weeks), according to irRECIST from the first dose date until disease progression/recurrence.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to a maximum of 54 months

Population: Full Analysis Set. Only those participants with data available at specified time point were analyzed.

PFS is defined as the time from first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression based on the time of first documentation of disease progression per RECIST v1.1. Progression is defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=53 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=55 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 2: Progression Free Survival (PFS) as Measured by RECIST v1.1	3.4 Months Interval 2.1 to 8.2	2.5 Months Interval 1.4 to 6.4

SECONDARY outcome

Timeframe: Up to a maximum of 54 months

Progression free survival is defined as the duration of time from the date of study enrollment until time of disease relapse, disease progression, or death, whichever comes first. Progression was to be assessed using the Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST). Immune related progressive disease (irPD) is defined as at least two consecutive radiographic determinations of progressive disease (PD - e.g., appearance of one or more new lesions) at least 4 weeks apart).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to a maximum of 54 months

Population: Full Analysis Set. Only those participants with data available at specified time point were analyzed.

OS is defined as the time from date of first dose of study treatment to the date of death by any cause.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=53 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=55 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 2: Overall Survival (OS)	17.1 Months Interval 7.9 to \<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.	9.4 Months Interval 3.2 to 22.2

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set comprised of all participants with sufficient data to enable estimation of at least one PK parameter. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points. Pharmacokinetic (PK) analysis of Niraparib was conducted using standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=6 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=6 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 (Predose) to 24 Hours Post Dose (AUC [0-24]) of Niraparib	6524.035 Hour*nanogram per milliliter Standard Deviation 2606.263	8855.687 Hour*nanogram per milliliter Standard Deviation 1415.318

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=3 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=2 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: AUC (0-24) of Major Metabolite of Niraparib (M1)	4886.115 Hour*nanogram per milliliter Standard Deviation 975.011	11076.538 Hour*nanogram per milliliter Standard Deviation 6691.358

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points. Pharmacokinetic analysis of Niraparib was conducted using standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=7 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=7 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Minimum Observed Plasma Concentration (Cmin) and Maximum Observed Plasma Concentration (Cmax) of Niraparib Cmin	174.00 Nanogram per milliliter Standard Deviation 84.922	205.63 Nanogram per milliliter Standard Deviation 196.714
Phase 1: Minimum Observed Plasma Concentration (Cmin) and Maximum Observed Plasma Concentration (Cmax) of Niraparib Cmax	546.0 Nanogram per milliliter Standard Deviation 195.95	711.3 Nanogram per milliliter Standard Deviation 189.98

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=7 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=7 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1) Cmin	42.114 Nanogram per milliliter Standard Deviation 42.765	46.677 Nanogram per milliliter Standard Deviation 45.343
Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1) Cmax	340.14 Nanogram per milliliter Standard Deviation 89.356	491.66 Nanogram per milliliter Standard Deviation 226.122

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. The current PK sampling schedule made the estimation of CL/F incalculable due to long half life of Niraparib.

Blood samples were planned to be collected for to determine CL/F of Niraparib.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=7 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=7 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Apparent Oral Clearance (CL/F) of Niraparib	NA Liters per hour Standard Deviation NA NA indicates that data was not available as the current PK sampling schedule made the estimation of CL/F incalculable due to long half-life of Niraparib.	NA Liters per hour Standard Deviation NA NA indicates that data was not available as the current PK sampling schedule made the estimation of CL/F incalculable due to long half-life of Niraparib.

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. The current PK sampling schedule made the estimation of CL/F incalculable due to long half life of major metabolite of Niraparib (M1).

Blood samples were planned to be collected for to determine CL/F of major metabolite (M1) of Niraparib.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=7 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=7 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Apparent Oral Clearance (CL/F) of Major Metabolite of Niraparib (M1)	NA Liters per hour Standard Deviation NA NA indicates that data was not available as the current PK sampling schedule made the estimation of CL/F incalculable due to long half-life of major metabolite of Niraparib (M1).	NA Liters per hour Standard Deviation NA NA indicates that data was not available as the current PK sampling schedule made the estimation of CL/F incalculable due to long half-life of major metabolite of Niraparib (M1).

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. The current PK sampling schedule made the estimation of Vz/F incalculable due to long half life of Niraparib.

Blood samples were planned to be collected for to determine Vz/F of Niraparib.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=7 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=7 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Volume of Distribution (Vz/F) of Niraparib	NA Liters Standard Deviation NA NA indicates that data was not available the current PK sampling schedule made the estimation of Vz/F incalculable due to long half-life of Niraparib.	NA Liters Standard Deviation NA NA indicates that data was not available the current PK sampling schedule made the estimation of Vz/F incalculable due to long half-life of Niraparib.

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. The current PK sampling schedule made the estimation of Vz/F incalculable due to long half life of major metabolite of Niraparib (M1).

Blood samples were planned to be collected for to determine Vz/F of major metabolite (M1) of Niraparib.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=7 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=7 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Volume of Distribution (Vz/F) of Major Metabolite of Niraparib (M1)	NA Liters Standard Deviation NA NA indicates that data was not available as the current PK sampling schedule made the estimation of Vz/F incalculable due to long half-life of major metabolite of Niraparib (M1).	NA Liters Standard Deviation NA NA indicates that data was not available as the current PK sampling schedule made the estimation of Vz/F incalculable due to long half-life of major metabolite of Niraparib (M1).

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points. Pharmacokinetic analysis of Niraparib was conducted using standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=4 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=2 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: AUC at Steady State (AUC,ss) of Niraparib	27396.910 Hour*nanograms per milliliter Standard Deviation 15097.186	30799.742 Hour*nanograms per milliliter Standard Deviation 9868.734

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=1 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=1 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: AUC,ss of Major Metabolite of Niraparib (M1)	32878.205 Hour*nanograms per milliliter Standard Deviation NA NA indicates that standard deviation could not be calculated for single participant.	127430.14 Hour*nanograms per milliliter Standard Deviation NA NA indicates that standard deviation could not be calculated for single participant.

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points. Pharmacokinetic analysis of Niraparib was conducted using standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=4 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=3 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Minimum Observed Plasma Concentration at Steady State (Cmin,ss) and Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Niraparib Cmin,ss	878.75 Nanograms per milliliter Standard Deviation 651.122	849.00 Nanograms per milliliter Standard Deviation 194.841
Phase 1: Minimum Observed Plasma Concentration at Steady State (Cmin,ss) and Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Niraparib Cmax,ss	1585.5 Nanograms per milliliter Standard Deviation 812.63	1606.7 Nanograms per milliliter Standard Deviation 261.02

SECONDARY outcome

Timeframe: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1(each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=4 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=3 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 1: Cmin,ss and Cmax,ss of Major Metabolite of Niraparib (M1) Cmin,ss	1410.000 Nanograms per milliliter Standard Deviation 207.686	3280.000 Nanograms per milliliter Standard Deviation 1460.411
Phase 1: Cmin,ss and Cmax,ss of Major Metabolite of Niraparib (M1) Cmax,ss	2177.50 Nanograms per milliliter Standard Deviation 475.000	4213.33 Nanograms per milliliter Standard Deviation 1515.333

SECONDARY outcome

Timeframe: Pre-dose and 2 Hours post-dose on Cycle 1 Day 1; Pre-dose and 2 Hours post-dose on Cycle 2 Day 1(each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected by sparse PK sampling to analyze plasma concentration of Niraparib.

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=50 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=54 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 2: Plasma Concentrations of Niraparib Cycle 1 Day 1: Predose	0.000 Nanograms per milliliter Standard Deviation 0.000	0.000 Nanograms per milliliter Standard Deviation 0.000
Phase 2: Plasma Concentrations of Niraparib Cycle 1 Day 1; 2 hours post dose	315.979 Nanograms per milliliter Standard Deviation 199.798	302.642 Nanograms per milliliter Standard Deviation 267.128
Phase 2: Plasma Concentrations of Niraparib Cycle 2 Day 1; Predose	441.978 Nanograms per milliliter Standard Deviation 229.948	510.154 Nanograms per milliliter Standard Deviation 263.634
Phase 2: Plasma Concentrations of Niraparib Cycle 2; Day 1; 2 hours post dose	764.500 Nanograms per milliliter Standard Deviation 370.140	884.185 Nanograms per milliliter Standard Deviation 508.607

SECONDARY outcome

Timeframe: Pre-dose and 2 Hours post-dose on Cycle 1 Day 1; Pre-dose and 2 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days)

Population: Pharmacokinetic Analysis Set. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected by sparse PK sampling to analyze plasma concentration of major metabolite of Niraparib (M1).

Outcome measures

Outcome measures
Measure	Phase 1: Niraparib 200 mg + Pembrolizumab n=50 Participants Participants received Niraparib 200 milligrams (mg) orally once daily from Days 1 to 21 and Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle.	Phase 1: Niraparib 300 mg + Pembrolizumab n=54 Participants Participants received Niraparib 300 mg orally once daily from Days 1 to 21 and Pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) Cycle 1 Day 1; Predose	0.000 Nanograms per milliliter Standard Deviation 0.000	0.000 Nanograms per milliliter Standard Deviation 0.000
Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) Cycle 1 Day1; 2 hours post dose	116.666 Nanograms per milliliter Standard Deviation 89.108	84.875 Nanograms per milliliter Standard Deviation 92.206
Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) Cycle 2 Day 1; Predose	1278.926 Nanograms per milliliter Standard Deviation 625.932	1070.923 Nanograms per milliliter Standard Deviation 648.225
Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) Cycle 2 Day 1; 2 hours post dose	1500.143 Nanograms per milliliter Standard Deviation 976.572	1205.444 Nanograms per milliliter Standard Deviation 858.698

Adverse Events

Phase 1: Niraparib 200 mg + Pembrolizumab

Serious events: 6 serious events

Other events: 7 other events

Deaths: 5 deaths

Phase 1: Niraparib 300 mg + Pembrolizumab

Serious events: 4 serious events

Other events: 7 other events

Deaths: 5 deaths

Phase 2 OC: Niraparib 200 mg + Pembrolizumab

Serious events: 22 serious events

Other events: 52 other events

Deaths: 30 deaths

Phase 2 TNBC: Niraparib 200 mg + Pembrolizumab

Serious events: 24 serious events

Other events: 54 other events

Deaths: 42 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER