Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Immune System Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Carcinoma

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

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

2:1 Ratio administered once daily continuously during a 28 day cycle.

Administered once daily continuously over a 28 day cycle.

Active comparator: Niraparib

placebo

GSK Clinical Studies

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of niraparib as maintenance in platinum sensitive ovarian cancer patients who have either gBRCAmut or a tumor with high-grade serous histology and who have responded to their most recent chemotherapy containing a platinum agent. Niraparib is an orally active PARP inhibitor. Niraparib or placebo (in a 2:1 ratio) will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI), European Quality of Life scale, 5-Dimensions (EQ-5D), and a neuropathy questionnaire. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.

The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in patients who have platinum sensitive ovarian cancer as assessed by the prolongation of progression free survival (PFS).

A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer

A Phase 3 Randomized Double-blind Trial of Maintenance With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer.

PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion.PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death.

The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death

Chemotherapy-Free Interval was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment

Progression-Free Survival 2 was defined as the date of randomization in the current study to the earlier date of assessment of progression on the next anti-cancer therapy following study treatment or death due to any cause. Progression was determined by the investigator via clinical and radiographic assessment using the same criteria as used in the current study.

Overall survival was defined as the date of randomization to the date of death by any cause.

TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death.

Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from "not at all" (0) to "very much" (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit"). Baseline was latest non-missing pre-dose assessment on or before randomization date.

A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of "not at all" (0) to "very much" (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 ("not at all") was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 ("a little bit").

This will never be analyzed since the data for the candidate companion BRAC analysis diagnostic test was not collected which was to be compared with centralized BRCA mutation test used in this study.

This will never be analyzed since the data for the candidate companion HRD diagnostic test was not collected which was to be compared with HRD test used in this study.

An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. Data presented for this outcome measure is based on the data cut-off date of 31-March-2021, which aligns with the time of the study unblinding.

An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. The data is presented for post-study unblinding duration 01-Apr-2021 to 26-Dec-2021

An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events.

Blood samples were collected at indicated time points to analyze AUC(0-infinity) of niraparib.

Blood samples were collected at indicated time points to analyze the AUC(0-last) of niraparib.

Blood samples were collected at indicated time points to analyze the maximum observed plasma concentration of niraparib.

Blood samples were collected at indicated time points to analyze the tmax of niraparib.

Blood samples were collected at indicated time points to analyze the t1/2 of niraparib.

12-lead electrocardiogram was obtained at indicated time points using an automated electrocardiogram machine that measured QTcF interval. The number of participants with maximum post-Baseline ECG value exceeding the following limits have been reported: QTcF interval \>450 and \<= 480 milliseconds (msec) and \>500 msec.

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Myriad Genetics, Inc.

US Oncology Research

Sarah Cannon

Cooperative Ovarian Cancer Group (COGI)

Facing Our Risk of Cancer Empowered

Tesaro, Inc.

Safety Population was used to assess SAEs and non-SAEs, which comprised of all participants who ingested any amount of study drug. The data is presented in separate arms for adverse events before unblinding (data cut-off date of 31-March-2021) and post-study unblinding until the end of study (01-April-2021 to 26-December-2021).

Participants with germline breast cancer gene (gBRCA) mutation received oral dose of niraparib 300 milligrams (mg) once daily in 28-day cycles until disease progression.

gBRCA Niraparib

Participants with germline BRCA mutation received oral dose of placebo matching niraparib once daily in 28-day cycles until disease progression

gBRCA Placebo

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Non-gBRCA Niraparib

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Non-gBRCA Placebo

Participants received Niraparib 300 mg in fasted condition

FE Niraparib Fasted

Participants received Niraparib 300 mg in fed condition

FE Niraparib Fed

Participants received Niraparib 300 mg once daily orally.

QTc Sub-study: Niraparib

Participants with germline breast cancer gene (gBRCA) mutation received oral dose of niraparib 300 milligrams (mg) once daily in 28-day cycles until disease progression. This arm presents data for post-study unblinding duration 01-Apr-2021 to 26-Dec-2021

gBRCA Niraparib (Post-study Unblinding [PSU])

Participants with germline BRCA mutation received oral dose of placebo matching niraparib once daily in 28-day cycles until disease progression. This arm presents data for post-study unblinding duration 01-Apr-2021 to 26-Dec-2021

gBRCA Placebo (PSU)

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression. This arm presents data for post-study unblinding duration 01-Apr-2021 to 26-Dec-2021

Non-gBRCA Niraparib (PSU)

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression. This arm presents data for post-study unblinding duration 01-Apr-2021 to 26-Dec-2021

Non-gBRCA Placebo (PSU)

Participants with germline BRCA mutation received oral dose of placebo matching niraparib once daily in 28-day cycles until disease progression.

Participants received a single dose of 3x100 mg capsules of niraparib administered orally following a minimum 10-hour overnight fast in Period 1 followed by 300 mg capsules of niraparib administered orally as single dose in fed condition (high-fat meal) in Period 2. There was a washout period of 7 days between treatment periods.

FE Sub-study: Fasted/Fed

Participants received single dose of 3x100 mg capsules of niraparib administered orally following a high-fat meal in Period 1 followed by 3x100 mg capsules of niraparib administered orally as single dose in fasted condition in Period 2. There was a washout period of 7 days between treatment periods.

FE Sub-study: Fed/Fasted

Total

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

The baseline analysis population was the intent-to-treat population, defined as all randomized participants with participants analyzed according to the study drug assigned via randomization

GSK Response Center

Intent-to-treat population was defined as all randomized participants with participants analyzed according to the study drug assigned via randomization

Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA)

Niraparib (300 mg) once daily in 28-day cycles until disease progression in participants with homologous recombination deficiency-positive (HRD+) tumors Niraparib vs. Placebo 2:1 ratio

Non-gBRCAmut HRD+ Niraparib

Placebo once daily in 28-day cycles until disease progression patients with homologous recombination deficiency-positive (HRD+) tumors Niraparib vs. Placebo 2:1 ratio

Non-gBRCAmut HRD+ Placebo

Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.

Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+)

Niraparib (300 mg) once daily in 28-day cycles until disease progression in patients without germline BRCA mutation Niraparib vs. Placebo 2:1 ratio

Placebo once daily in 28-day cycles until disease progression in patients without germline BRCA mutation Niraparib vs. Placebo 2:1 ratio

Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation

Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)

Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation

Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA)

Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation

Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA)

Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation

Overall Survival in Cohort With Germline BRCA Mutation (gBRCA)

Overall Survival in Cohort With No Germline BRCA Mutation

Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)

Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Post-progression

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Post-progression

Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2

Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4

Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6

Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Post-progression

Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2

Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4

Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6

Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Post-progression

Feet, 0-Not at all

Feet, 1-A little bit

Feet, 2-Somewhat

Feet, 3-Quite a bit

Feet, 4-Very much

Hands, 0-Not at all

Hands, 1-A little bit

Hands, 2-Somewhat

Hands, 3-Quite a bit

Hands, 4-Very much

Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline

Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2

Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4

Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6

Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression

Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline

Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2

Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4

Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6

Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression

Number of Participants With Concordance of a Candidate Companion BRAC Analysis Diagnostic Test Compared to the Centralized BRCA Mutation Test Used in This Study

Number of Participants With Concordance of a Candidate Companion HRD Diagnostic Test Compared to the HRD Test Used in This Study

Non-serious AEs

SAEs

Safety Population consisted of all participants who ingested any amount of study drug.

Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)

Participants with germline breast cancer gene (gBRCA) mutation received oral dose of niraparib 300 milligrams (mg) once daily in 28-day cycles until disease progression. This arm presents data for post-study unblinding duration 1-Apr-2021 to 26-Dec-2021.

gBRCA Niraparib (PSU)

Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding)

Number of Participants With Non-serious AEs and SAEs in FE Sub-study

Number of Participants With Non-serious AEs and SAEs in QTc Sub-study

Pharmacokinetic population consisted of all participants who received at least one dose of study drug, with sufficient data available to calculate parameters. Only those participants with data available at the specified time points were analyzed.

Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-infinity]) Following Administration of Niraparib (FE Sub-study)

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

Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-last]) Following Administration of Niraparib (FE Sub-study)

Spots Global Cancer Trial Database for active comparator: niraparib