Advanced Breast Cancer, Breast Cancer, Fallopian Tube Cancer, Metastatic Breast Cancer, Neoplasms, Ovarian Cancer, Peritoneal Cancer, Stage IV Breast Cancer, Triple Negative Breast Cancer
Conditions
Keywords
PARP inhibitor, PD-1, Niraparib, Pembrolizumab, Keynote, TOPACIO
Brief summary
This Phase 1/2 study will evaluate the safety and efficacy of combination treatment with niraparib and pembrolizumab (MK-3475) in patients with advanced or metastatic triple-negative breast cancer or recurrent ovarian cancer. (KEYNOTE-162)
Interventions
DRUGniraparib
BIOLOGICALpembrolizumab
Sponsors
Merck Sharp & Dohme LLC
Tesaro, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Patient has histologically proven advanced (unresectable) or metastatic cancer as outlined below according to study phase and disease type: 1. Phase 1 patients (breast or ovarian cancer) * Patients with advanced or metastatic breast cancer must have disease that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative (ie, TNBC). Patients with advanced or metastatic disease may have up to 4 lines of cytotoxic therapy. Neoadjuvant and adjuvant therapies are not counted towards lines of therapy. * Patients must have any epithelial (ie, serous, endometroid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer. Patients must have experienced a response lasting at least 6 months to first-line platinum-based therapy but currently considered to have platinum-resistant disease per investigator's assessment (e.g, patient is not eligible for further platinum containing treatment). Patients may have received up to 5 lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant and adjuvant therapies are not counted towards lines of therapy. 2. Phase 2 patients (breast or ovarian cancer) * Patients with advanced or metastatic breast cancer must have TNBC. Patients with advanced or metastatic disease may have received up to 2 lines of cytotoxic therapy. Adjuvant and/or neoadjuvant therapies are not counted in the number of lines of therapy. TNBC patients who have previously received platinum chemotherapy in the metastatic setting are allowed to enroll in the study as long as they did not progress while on or within 8 weeks from the day of the last platinum administration. * Patients must have with high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer. Patients must have experienced a response lasting at least 6 months to first-line platinum-based therapy but currently considered to have platinum-resistant disease per investigator's assessment (e.g, patient is not eligible for further platinum containing treatment). Patients may have had up to 4 lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant, adjuvant, and the combination of both will be considered as one line of therapy. * Archival tumor tissue available or a fresh biopsy must be obtained prior to study treatment initiation * Measurable lesions by RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) 0 or 1 * Adequate organ function * Able to take oral medications * Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours of taking study medication and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment * Male patient agrees to use an adequate method of contraception Main
Exclusion criteria
* Patients with primary platinum refractory ovarian cancer (ie, progressive disease on or within 6 months of first-line platinum therapy) * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Note: Patients previously treated for brain metastases may be able to participate provided they are stable * Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer * Poor medical risk * Condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment. * Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study * Immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment * Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) * Known active hepatitis B or hepatitis C * Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment * Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent * Prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor * Heart-rate corrected QT interval (QTc) prolongation \> 470 msec at screening * Known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants Reporting Dose-Limiting Toxicities (DLTs) | During Cycle 1, ie, during the first 21 days of treatment | 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. |
| Phase 2: Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | Up to 40 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Overall Response Rate (ORR) as Measured by Immune-related RECIST (irRECIST) | Up to a maximum of 54 months | 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). |
| Phase 2: Duration of Response (DOR) as Measured by RECIST v1.1 | Up to a maximum of 54 months | 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. |
| Phase 2: DOR as Measured by irRECIST | 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). |
| Phase 2: Disease Control Rate (DCR) as Measured by RECIST v1.1 | Up to 40 weeks | 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. |
| Phase 2: DCR as Measured by irRECIST | 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. |
| Phase 2: Progression Free Survival (PFS) as Measured by RECIST v1.1 | Up to a maximum of 54 months | 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. |
| Phase 2: PFS as Measured by irRECIST | 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). |
| Phase 2: Overall Survival (OS) | Up to a maximum of 54 months | OS is defined as the time from date of first dose of study treatment to the date of death by any cause. |
| Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 (Predose) to 24 Hours Post Dose (AUC [0-24]) of Niraparib | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days) | Blood samples were collected at indicated time points. Pharmacokinetic (PK) analysis of Niraparib was conducted using standard non-compartmental analysis. |
| Phase 1: AUC (0-24) of Major Metabolite of Niraparib (M1) | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days) | Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis. |
| Phase 1: Minimum Observed Plasma Concentration (Cmin) and Maximum Observed Plasma Concentration (Cmax) of Niraparib | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days) | Blood samples were collected at indicated time points. Pharmacokinetic analysis of Niraparib was conducted using standard non-compartmental analysis. |
| Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to a maximum of 22 months | 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. |
| Phase 1: Apparent Oral Clearance (CL/F) of Niraparib | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days) | Blood samples were planned to be collected for to determine CL/F of Niraparib. |
| Phase 1: Apparent Oral Clearance (CL/F) of Major Metabolite of Niraparib (M1) | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days) | Blood samples were planned to be collected for to determine CL/F of major metabolite (M1) of Niraparib. |
| Phase 1: Volume of Distribution (Vz/F) of Niraparib | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days) | Blood samples were planned to be collected for to determine Vz/F of Niraparib. |
| Phase 1: Volume of Distribution (Vz/F) of Major Metabolite of Niraparib (M1) | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days) | Blood samples were planned to be collected for to determine Vz/F of major metabolite (M1) of Niraparib. |
| Phase 1: AUC at Steady State (AUC,ss) of Niraparib | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days) | Blood samples were collected at indicated time points. Pharmacokinetic analysis of Niraparib was conducted using standard non-compartmental analysis. |
| Phase 1: AUC,ss of Major Metabolite of Niraparib (M1) | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days) | Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis. |
| Phase 1: Minimum Observed Plasma Concentration at Steady State (Cmin,ss) and Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Niraparib | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days) | Blood samples were collected at indicated time points. Pharmacokinetic analysis of Niraparib was conducted using standard non-compartmental analysis. |
| Phase 1: Cmin,ss and Cmax,ss of Major Metabolite of Niraparib (M1) | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1(each cycle of 21 days) | Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis. |
| Phase 2: Plasma Concentrations of Niraparib | 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) | Blood samples were collected by sparse PK sampling to analyze plasma concentration of Niraparib. |
| Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) | 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) | Blood samples were collected by sparse PK sampling to analyze plasma concentration of major metabolite of Niraparib (M1). |
| Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1) | Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days) | Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis. |
| Phase 2: Number of Participants With TEAEs | Up to a maximum of 54 months | 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. |
Countries
United States
Participant flow
Recruitment details
This was a multicenter study conducted in the United States.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| 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. | 7 |
| 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. | 53 |
| 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. | 55 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 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) | Radiologic Disease Progression | 0 | 1 | 0 | 0 |
| Phase 1: (Up to a Maximum of 22 Months) | Sponsor decision | 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) | Participant request | 0 | 0 | 2 | 1 |
| Phase 2: (Up to a Maximum of 54 Months) | Participants went on Rollover Study | 0 | 0 | 0 | 4 |
| Phase 2: (Up to a Maximum of 54 Months) | Physician Decision | 0 | 0 | 0 | 1 |
| 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) | Sponsor decision | 0 | 0 | 2 | 2 |
| Phase 2: (Up to a Maximum of 54 Months) | Withdrawal by Subject | 0 | 0 | 8 | 2 |
Baseline characteristics
| Characteristic | Phase 1: Niraparib 200 mg + Pembrolizumab | Total | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 1: Niraparib 300 mg + Pembrolizumab |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 30 Participants | 8 Participants | 16 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 92 Participants | 47 Participants | 37 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 7 Participants | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 113 Participants | 51 Participants | 50 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 5 Participants | 2 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 9 Participants | 8 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | NA Participants | NA Participants | NA Participants | NA Participants | NA Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 2 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 103 Participants | 43 Participants | 46 Participants | 7 Participants |
| Region of Enrollment United States | 7 Participants | 122 Participants | 55 Participants | 53 Participants | 7 Participants |
| Sex: Female, Male Female | 7 Participants | 122 Participants | 55 Participants | 53 Participants | 7 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 7 | 5 / 7 | 30 / 53 | 42 / 55 |
| other Total, other adverse events | 7 / 7 | 7 / 7 | 52 / 53 | 54 / 55 |
| serious Total, serious adverse events | 6 / 7 | 4 / 7 | 22 / 53 | 24 / 55 |
Outcome results
Primary
Phase 1: Number of Participants Reporting Dose-Limiting Toxicities (DLTs)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Number of Participants Reporting Dose-Limiting Toxicities (DLTs) | 1 Participants |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Number of Participants Reporting Dose-Limiting Toxicities (DLTs) | 1 Participants |
Primary
Phase 2: Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
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.
Time frame: 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. .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | 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 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | 18.2 Percentage of participants |
Secondary
Phase 1: Apparent Oral Clearance (CL/F) of Major Metabolite of Niraparib (M1)
Blood samples were planned to be collected for to determine CL/F of major metabolite (M1) of Niraparib.
Time frame: 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).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Apparent Oral Clearance (CL/F) of Major Metabolite of Niraparib (M1) | NA Liters per hour |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Apparent Oral Clearance (CL/F) of Major Metabolite of Niraparib (M1) | NA Liters per hour |
Secondary
Phase 1: Apparent Oral Clearance (CL/F) of Niraparib
Blood samples were planned to be collected for to determine CL/F of Niraparib.
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Apparent Oral Clearance (CL/F) of Niraparib | NA Liters per hour |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Apparent Oral Clearance (CL/F) of Niraparib | NA Liters per hour |
Secondary
Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 (Predose) to 24 Hours Post Dose (AUC [0-24]) of Niraparib
Blood samples were collected at indicated time points. Pharmacokinetic (PK) analysis of Niraparib was conducted using standard non-compartmental analysis.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | 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 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 (Predose) to 24 Hours Post Dose (AUC [0-24]) of Niraparib | 8855.687 Hour*nanogram per milliliter | Standard Deviation 1415.318 |
Secondary
Phase 1: AUC (0-24) of Major Metabolite of Niraparib (M1)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: AUC (0-24) of Major Metabolite of Niraparib (M1) | 4886.115 Hour*nanogram per milliliter | Standard Deviation 975.011 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: AUC (0-24) of Major Metabolite of Niraparib (M1) | 11076.538 Hour*nanogram per milliliter | Standard Deviation 6691.358 |
Secondary
Phase 1: AUC at Steady State (AUC,ss) of Niraparib
Blood samples were collected at indicated time points. Pharmacokinetic analysis of Niraparib was conducted using standard non-compartmental analysis.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: AUC at Steady State (AUC,ss) of Niraparib | 27396.910 Hour*nanograms per milliliter | Standard Deviation 15097.186 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: AUC at Steady State (AUC,ss) of Niraparib | 30799.742 Hour*nanograms per milliliter | Standard Deviation 9868.734 |
Secondary
Phase 1: AUC,ss of Major Metabolite of Niraparib (M1)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis.
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: AUC,ss of Major Metabolite of Niraparib (M1) | 32878.205 Hour*nanograms per milliliter |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: AUC,ss of Major Metabolite of Niraparib (M1) | 127430.14 Hour*nanograms per milliliter |
Secondary
Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1) | Cmin | 42.114 Nanogram per milliliter | Standard Deviation 42.765 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1) | Cmax | 340.14 Nanogram per milliliter | Standard Deviation 89.356 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1) | Cmin | 46.677 Nanogram per milliliter | Standard Deviation 45.343 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1) | Cmax | 491.66 Nanogram per milliliter | Standard Deviation 226.122 |
Secondary
Phase 1: Cmin,ss and Cmax,ss of Major Metabolite of Niraparib (M1)
Blood samples were collected at indicated time points. Pharmacokinetic analysis of major metabolite of Niraparib (M1) was conducted using standard non-compartmental analysis.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Cmin,ss and Cmax,ss of Major Metabolite of Niraparib (M1) | Cmin,ss | 1410.000 Nanograms per milliliter | Standard Deviation 207.686 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Cmin,ss and Cmax,ss of Major Metabolite of Niraparib (M1) | Cmax,ss | 2177.50 Nanograms per milliliter | Standard Deviation 475 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Cmin,ss and Cmax,ss of Major Metabolite of Niraparib (M1) | Cmin,ss | 3280.000 Nanograms per milliliter | Standard Deviation 1460.411 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Cmin,ss and Cmax,ss of Major Metabolite of Niraparib (M1) | Cmax,ss | 4213.33 Nanograms per milliliter | Standard Deviation 1515.333 |
Secondary
Phase 1: Minimum Observed Plasma Concentration at Steady State (Cmin,ss) and Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Niraparib
Blood samples were collected at indicated time points. Pharmacokinetic analysis of Niraparib was conducted using standard non-compartmental analysis.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | 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 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | 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 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | 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 | 849.00 Nanograms per milliliter | Standard Deviation 194.841 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | 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 | 1606.7 Nanograms per milliliter | Standard Deviation 261.02 |
Secondary
Phase 1: Minimum Observed Plasma Concentration (Cmin) and Maximum Observed Plasma Concentration (Cmax) of Niraparib
Blood samples were collected at indicated time points. Pharmacokinetic analysis of Niraparib was conducted using standard non-compartmental analysis.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | 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 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | 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 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Minimum Observed Plasma Concentration (Cmin) and Maximum Observed Plasma Concentration (Cmax) of Niraparib | Cmin | 205.63 Nanogram per milliliter | Standard Deviation 196.714 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Minimum Observed Plasma Concentration (Cmin) and Maximum Observed Plasma Concentration (Cmax) of Niraparib | Cmax | 711.3 Nanogram per milliliter | Standard Deviation 189.98 |
Secondary
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
Secondary
Phase 1: Volume of Distribution (Vz/F) of Major Metabolite of Niraparib (M1)
Blood samples were planned to be collected for to determine Vz/F of major metabolite (M1) of Niraparib.
Time frame: 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).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Volume of Distribution (Vz/F) of Major Metabolite of Niraparib (M1) | NA Liters |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Volume of Distribution (Vz/F) of Major Metabolite of Niraparib (M1) | NA Liters |
Secondary
Phase 1: Volume of Distribution (Vz/F) of Niraparib
Blood samples were planned to be collected for to determine Vz/F of Niraparib.
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 1: Volume of Distribution (Vz/F) of Niraparib | NA Liters |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 1: Volume of Distribution (Vz/F) of Niraparib | NA Liters |
Secondary
Phase 2: DCR as Measured by irRECIST
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.
Time frame: 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.
Secondary
Phase 2: Disease Control Rate (DCR) as Measured by RECIST v1.1
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.
Time frame: Up to 40 weeks
Population: Full Analysis Set. Only those participants with data available at specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Disease Control Rate (DCR) as Measured by RECIST v1.1 | 58.5 Percentage of participants |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Disease Control Rate (DCR) as Measured by RECIST v1.1 | 41.8 Percentage of participants |
Secondary
Phase 2: DOR as Measured by irRECIST
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).
Time frame: 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.
Secondary
Phase 2: Duration of Response (DOR) as Measured by RECIST v1.1
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.
Time frame: Up to a maximum of 54 months
Population: Full Analysis Set. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Duration of Response (DOR) as Measured by RECIST v1.1 | 14.4 Months |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Duration of Response (DOR) as Measured by RECIST v1.1 | 21.5 Months |
Secondary
Phase 2: Number of Participants With TEAEs
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.
Time frame: Up to a maximum of 54 months
Population: Safety Analysis Set. Only those participants with data available at specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Number of Participants With TEAEs | 53 Participants |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Number of Participants With TEAEs | 54 Participants |
Secondary
Phase 2: Overall Response Rate (ORR) as Measured by Immune-related RECIST (irRECIST)
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).
Time frame: 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.
Secondary
Phase 2: Overall Survival (OS)
OS is defined as the time from date of first dose of study treatment to the date of death by any cause.
Time frame: Up to a maximum of 54 months
Population: Full Analysis Set. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Overall Survival (OS) | 17.1 Months |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Overall Survival (OS) | 9.4 Months |
Secondary
Phase 2: PFS as Measured by irRECIST
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).
Time frame: 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.
Secondary
Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1)
Blood samples were collected by sparse PK sampling to analyze plasma concentration of major metabolite of Niraparib (M1).
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) | Cycle 1 Day 1; Predose | 0.000 Nanograms per milliliter | Standard Deviation 0 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | 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 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) | Cycle 2 Day 1; Predose | 1278.926 Nanograms per milliliter | Standard Deviation 625.932 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | 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 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) | Cycle 2 Day 1; 2 hours post dose | 1205.444 Nanograms per milliliter | Standard Deviation 858.698 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) | Cycle 1 Day 1; Predose | 0.000 Nanograms per milliliter | Standard Deviation 0 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) | Cycle 2 Day 1; Predose | 1070.923 Nanograms per milliliter | Standard Deviation 648.225 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1) | Cycle 1 Day1; 2 hours post dose | 84.875 Nanograms per milliliter | Standard Deviation 92.206 |
Secondary
Phase 2: Plasma Concentrations of Niraparib
Blood samples were collected by sparse PK sampling to analyze plasma concentration of Niraparib.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Niraparib | Cycle 1 Day 1: Predose | 0.000 Nanograms per milliliter | Standard Deviation 0 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Niraparib | Cycle 1 Day 1; 2 hours post dose | 315.979 Nanograms per milliliter | Standard Deviation 199.798 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Niraparib | Cycle 2 Day 1; Predose | 441.978 Nanograms per milliliter | Standard Deviation 229.948 |
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Niraparib | Cycle 2; Day 1; 2 hours post dose | 764.500 Nanograms per milliliter | Standard Deviation 370.14 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Niraparib | Cycle 2; Day 1; 2 hours post dose | 884.185 Nanograms per milliliter | Standard Deviation 508.607 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Niraparib | Cycle 1 Day 1: Predose | 0.000 Nanograms per milliliter | Standard Deviation 0 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Niraparib | Cycle 2 Day 1; Predose | 510.154 Nanograms per milliliter | Standard Deviation 263.634 |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Plasma Concentrations of Niraparib | Cycle 1 Day 1; 2 hours post dose | 302.642 Nanograms per milliliter | Standard Deviation 267.128 |
Secondary
Phase 2: Progression Free Survival (PFS) as Measured by RECIST v1.1
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.
Time frame: Up to a maximum of 54 months
Population: Full Analysis Set. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Niraparib 200 mg + Pembrolizumab | Phase 2: Progression Free Survival (PFS) as Measured by RECIST v1.1 | 3.4 Months |
| Phase 1: Niraparib 300 mg + Pembrolizumab | Phase 2: Progression Free Survival (PFS) as Measured by RECIST v1.1 | 2.5 Months |