Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Fallopian Tube Neoplasms

Breast Diseases

Skin Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Niraparib

Pembrolizumab

Poly(ADP-ribose) Polymerase Inhibitors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

Phase 1: Dose-escalation: ascending doses of niraparib up to 300mg/day orally (PO) on Days 1-21 and pembrolizumab 200mg intravenously (IV) on Day 1 of each 21-day cycle

Phase 2: niraparib (recommended Phase 2 dose) in combination with pembrolizumab 200mg IV on Day 1 of each 21-day cycle

niraparib

pembrolizumab

GSK Clinical Trials

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)

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

Phase 1/2 Clinical Study of Niraparib in Combination With Pembrolizumab (MK-3475) in Patients With Advanced or Metastatic Triple-Negative Breast Cancer and in Patients With Recurrent Ovarian Cancer

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.

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.

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.

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).

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.

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).

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.

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.

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.

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).

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

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

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

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

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

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

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

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

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

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

Merck Sharp & Dohme LLC

Tesaro, Inc.

All-cause mortality, SAE and non-SAE were collected in Safety analysis set which comprised of all participants who received any amount of study treatment in Phase 1 or Phase 2.

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 200 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 1: Niraparib 300 mg + 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 OC: Niraparib 200 mg + 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 2 TNBC: Niraparib 200 mg + Pembrolizumab

Phase 2 OC: Niraparib 200mg + Pembrolizumab

Phase 2 TNBC: Niraparib 200mg + Pembrolizumab

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

The Baseline analysis Population consisted of all participants who received at least one dose of study medication.

GSK Response Center

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.

Phase 1: Number of Participants Reporting Dose-Limiting Toxicities (DLTs)

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. .

Phase 2: Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1

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.

Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

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

Phase 2: Number of Participants With TEAEs

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.

Phase 2: Overall Response Rate (ORR) as Measured by Immune-related RECIST (irRECIST)

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

Phase 2: Duration of Response (DOR) as Measured by RECIST v1.1

Phase 2: DOR as Measured by irRECIST

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

Phase 2: Disease Control Rate (DCR) as Measured by RECIST v1.1

Phase 2: DCR as Measured by irRECIST

Phase 2: Progression Free Survival (PFS) as Measured by RECIST v1.1

Phase 2: PFS as Measured by irRECIST

Phase 2: Overall Survival (OS)

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.

Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 (Predose) to 24 Hours Post Dose (AUC [0-24]) of Niraparib

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

Phase 1: AUC (0-24) of Major Metabolite of Niraparib (M1)

Cmin

Cmax

Phase 1: Minimum Observed Plasma Concentration (Cmin) and Maximum Observed Plasma Concentration (Cmax) of Niraparib

Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1)

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

Phase 1: Apparent Oral Clearance (CL/F) of Niraparib

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).

Phase 1: Apparent Oral Clearance (CL/F) of Major Metabolite of Niraparib (M1)

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

Phase 1: Volume of Distribution (Vz/F) of Niraparib

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).

Phase 1: Volume of Distribution (Vz/F) of Major Metabolite of Niraparib (M1)

Phase 1: AUC at Steady State (AUC,ss) of Niraparib

Phase 1: AUC,ss of Major Metabolite of Niraparib (M1)

Cmin,ss

Cmax,ss

Phase 1: Minimum Observed Plasma Concentration at Steady State (Cmin,ss) and Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Niraparib

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer	NCT02657889	Neoplasms Triple Negative... Ovarian Cancer Breast Cancer Metastatic Brea... Advanced Breast... Stage IV Breast... Fallopian Tube ... Peritoneal Canc...	niraparib pembrolizumab	18 Years -	Tesaro, Inc.
Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer	NCT02657889	Neoplasms Triple Negative... Ovarian Cancer Breast Cancer Metastatic Brea... Advanced Breast... Stage IV Breast... Fallopian Tube ... Peritoneal Canc...	niraparib pembrolizumab	18 Years -	Tesaro, Inc.

Spots Global Cancer Trial Database for topacio

Every month we try and update this database with for topacio cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for topacio

Every month we try and update this database with for topacio cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for topacio cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.