Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03602859 | A Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer | PHASE3 | ACTIVE NOT_RECRUITING | 1,400 | — | — | Oct 11, 2018 | Apr 30, 2029 | Dec 31, 2025 | 182 | United States, Belarus +17 |
| NCT02655016 | A Study of Niraparib (GSK3985771) Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy | PHASE3 | ACTIVE NOT_RECRUITING | 733 | — | — | Jul 11, 2016 | May 29, 2026 | Mar 10, 2026 | 116 | United States, Belgium +12 |
| NCT04641247 | A Long-term Treatment Extension Study of Niraparib in Participants Who Completed a Prior GlaxoSmithKline/TESARO-sponsored Niraparib Study | PHASE2 | RECRUITING | 30 | — | — | Apr 16, 2021 | Nov 13, 2026 | Sep 29, 2025 | 25 | United States, Austria +6 |
| NCT03574779 | A Study to Evaluate the Efficacy and Safety of Novel Treatment Combinations in Participants With Ovarian Cancer | PHASE2 | COMPLETED | 77 | — | — | Nov 15, 2018 | Mar 31, 2025 | Jul 15, 2025 | 28 | United States, Canada +1 |
| NCT03326193 | A Study of Niraparib Combined With Bevacizumab Maintenance Treatment in Participants With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy | PHASE2 | COMPLETED | 105 | — | — | Dec 12, 2017 | Jul 12, 2024 | Jul 31, 2025 | 29 | United States |
| NCT02354586 | A Study of Niraparib in Patients With Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens | PHASE2 | COMPLETED | 463 | — | — | Mar 23, 2015 | Aug 23, 2021 | Sep 15, 2022 | 55 | United States, Canada |
| NCT03359850 | Pharmacokinetic and Safety Study of Niraparib With Normal or Moderate Hepatic Impairment Patients | PHASE1 | COMPLETED | 17 | — | — | Feb 20, 2018 | Jun 24, 2020 | May 28, 2021 | 5 | United States |
Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of first documented progressive disease (PD) or death due to any cause, whichever occurs first by the Investigator assessment according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1. Progressive Disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeter (mm).
Progression free survival was defined as the time from the date of treatment randomization to the date of first documentation of disease progression or death due to any cause in the absence of documented progression, whichever occurs first. It was assessed by the blinded independent central review (BICR). Median and 95% confidence interval (CI) are presented.
AEs, SAEs and AESI will be collected.
The performance status will be assessed using ECOG scale, where Grade 0 (fully active), Grade 1 (restricted in physically strenuous activity), Grade 2 (ambulatory and capable of all self-care), Grade 3 (capable of only limited self-care) and Grade 4 (completely disabled). Number of participants with clinically significant changes in ECOG performance status will be summarized.
Blood samples will be collected for the analysis of hematology and clinical chemistry parameters.
Number of participants with clinically significant changes in vital signs will be assessed.
Number of participants with clinically significant changes in physical examination will be assessed.
Number of participants using concomitant medications will be assessed.
Number of Participants enrolled across cohorts are presented.
PFS rate at 18 months is defined as the percentage of participants who have not progressed or died within 18 months after niraparib combined with bevacizumab treatment initiation. Progression was assessed by response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria per Investigator assessment and defined as a 20 percent (%) increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions. Survival rate is the percentage of participants without progression assessed by RECIST v1.1 or death by the landmark timepoint. Confidence intervals was constructed using exact method.
The ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) (version1.1), where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis, PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Primary Analysis Population comprised of participants who received 3 or 4 prior lines of therapy (LOT), had homologous recombination deficiency positive (HRDpos) tumors, had platinum-sensitive disease, and were poly(adenosine 5'-diphosphate \[ADP\]-ribose) polymerase inhibitors (PARPi) naïve.
Blood samples were collected at indicated time points to evaluate AUC (last) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points to evaluate AUC (0-infinity) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points to evaluate Cmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points to evaluate tmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Blood samples were collected at indicated time points to evaluate t1/2 of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
CL/F is calculated as Dose/(AUC 0-inf). Blood samples were collected at indicated time points to evaluate CL/F of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. Not applicable (NA) indicates that CL/F could not be measured for M1 since the dose of metabolite is unknown and only known dose is that of parent niraparib.
| Arm | Type | Description |
|---|---|---|
| Participants receiving SOC+placebo | PLACEBO_COMPARATOR | Participants in this arm will receive SOC (carboplatin+paclitaxel+/-bevacizumab) in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment with dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/-bevacizumab along with niraparib placebo and dostarlimab placebo |
| Participants receiving SOC+niraparib | ACTIVE_COMPARATOR | Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/- bevacizumab with niraparib and dostarlimab placebo |
| Participants receiving SOC+dostarlimab+niraparib | EXPERIMENTAL | Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab, and maintenance treatment of +/-bevacizumab with niraparib and dostarlimab |
| Participants receiving Niraparib | EXPERIMENTAL | - |
| Participants receiving Placebo | PLACEBO_COMPARATOR | - |
| Cohort A: 1-2 prior lines of therapy (TSR-042, Bevacizumab, and Niraparib) | EXPERIMENTAL | PARP Inhibitor-Naive Platinum-Resistant Ovarian Cancer Treatment Cohort with TSR-042, Bevacizumab, and Niraparib. TSR-042 administered 500 milligrams (mg) on Day 1 every 3 weeks (Q3W) for 4 cycles (each cycle is 21 days), followed by 1000 mg every 6 weeks (Q6W) beginning on Cycle 5 Day 1 until progressive disease (PD) or toxicity. Bevacizumab administered 15 milligram per kilogram (mg/kg) every 3 weeks for up to 15 months. Niraparib 200 or 300 mg per day until PD or toxicity. |
| Cohort C: Arm 1: Participants receiving platinum plus taxane | ACTIVE_COMPARATOR | Participants are expected to receive 1 run-in cycle (up to 5 weeks) of carboplatin-paclitaxel during pre-screening. After confirmation that the tumor is homologous recombination-deficient (HRd). Participants will then be randomized to three 21-day cycles of platinum-taxane doublet chemotherapy (carboplatin plus paclitaxane). After interval debulking surgery (IDS), all participants will receive up to three 21-day cycles of adjuvant platinum-taxane doublet chemotherapy (and optional bevacizumab for participants deemed high-risk; third cycle is optional) followed by niraparib (and optional bevacizumab or bevacizumab biosimilar for participants deemed high- risk) maintenance treatment. |
| Cohort C: Arm 2: Participants receiving neoadjuvant Niraparib | EXPERIMENTAL | Participants are expected to receive 1 run-in cycle (up to 5 weeks) of carboplatin-paclitaxel during pre-screening. After confirmation that the tumor is HRd, participants will be randomized to three 21-day cycles of neoadjuvant niraparib therapy. After IDS, all participants will receive up to three 21-day cycles of adjuvant platinum-taxane doublet chemotherapy (and optional bevacizumab for participants deemed high-risk; third cycle is optional) followed by niraparib (and optional bevacizumab or bevacizumab biosimilar for participants deemed high- risk) maintenance treatment. |
| Participants receiving niraparib+ bevacizumab | EXPERIMENTAL | Participants will be administered bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute (min) intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib will be administered orally once a day continuously throughout each 21-day cycle (84-day cycle after amendment 2). On Day 1 of each cycle, niraparib will be administered upon completion of bevacizumab infusion. The starting dose of niraparib will be based on the participant's Baseline actual body weight or platelet count. |
| Niraparib | EXPERIMENTAL | - |
| Normal hepatic function (Group 1): | EXPERIMENTAL | To evaluate the pharmocokinetics and safety of niraparib |
| Moderate hepatic impairment (Group 2): | EXPERIMENTAL | To evaluate the pharmocokinetics and safety of niraparib |
| Name | Type | Description |
|---|---|---|
| Niraparib | DRUG | Participants will receive oral capsules of niraparib as a unit dosage strength of 100 milligrams (mg) |
| Dostarlimab (TSR-042) | DRUG | Participants will receive 500 mg dostarlimab on day 1 every 3 weeks from cycle 2 to 6 followed by 1000mg of dostarlimab on day 1 every 6 weeks to continue up to 3 years in the absence of disease progression, unacceptable toxicity, participant withdrawal, or investigator decision |
| Standard of care | DRUG | Participants will receive SOC that includes paclitaxel 175 milligrams per square meter (mg/m\^2) on day 1 every 21 days + carboplatin area under the curve (AUC) of 5 to 6 milligrams per milliliter per minute (mg/mL/min) on day 1 every 21 days +/- bevacizumab 7.5 milligrams per kilograms (mg/kg) every 21 days or 15 mg/kg every 21 days for a total of 15 months. |
| Dostarlimab-Placebo | DRUG | Participants will receive 500 mg of dostarlimab-placebo on day 1 every 3 weeks from cycle 2 to 6 followed by 1000 mg of dostarlimab-placebo on day 1 every 6 weeks to continue up to 3 years in the absence of disease progression, unacceptable toxicity, participant withdrawal, or investigator decision |
| Niraparib-Placebo | DRUG | Participants will receive oral capsules of niraparib-placebo as a unit dosage strength of 100 mg. |
| Placebo | DRUG | Placebo will be administered. |
| TSR-042 | BIOLOGICAL | TSR-042 is a humanized monoclonal antibody that binds with high affinity to Programmed cell death protein 1 (PD-1) resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2). |
| Bevacizumab | BIOLOGICAL | Bevacizumab is an Food Drug and Administration (FDA) approved antiangiogenic recombinant humanized monoclonal Immunoglobulin (Ig) G1 antibody against the vascular endothelial growth factor protein, which has been shown to be efficacious against a variety of different cancer types, including colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. |
| Carboplatin | DRUG | Carboplatin will be infused intravenously over 60 minutes at the prescribed dose of area under the concentration versus time curve of 5 to 6 mg/milliliters (mL) per minute on Day 1 of every 21-day cycle |
| Paclitaxel | DRUG | Paclitaxel will be administered intravenously over 180 minutes at the prescribed dose of 175 mg/meter square (m\^2) on Day 1 of every 21-day cycle |
Inclusion criteria: * Participants must be female, \>=18 years of age, able to understand the study procedures, and agree to participate in the study by providing written informed consent. * Participants with a histologically confirmed diagnosis of high-grade nonmucinous epithelial ovarian (serous,...