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
FIRST
A Randomized, Double-blind, Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer
2 other identifiers
interventional
1,400
18 countries
181
Brief Summary
Ovarian cancer is a heterogeneous disease, characterized by complex molecular and genetic changes. The high expression of vascular endothelial growth factor (VEGF) receptor, programmed death receptor ligands 1 (PD-L1) expression, and deoxyribonucleic acid (DNA) damage in ovarian tumors provide several targets for treatment and maintenance of disease response. Given the unmet medical need of participants with advanced or metastatic ovarian cancer, this study design will enable investigators to provide participants with current SOC for ovarian cancer for the duration of the study. This is a global, multicenter, randomized, double-blind, controlled Phase 3 study that will primarily compare the progression-free survival (PFS) for participants receiving dostarlimab with SOC chemotherapy +/- bevacizumab followed by niraparib and dostarlimab maintenance +/- bevacizumab versus participants receiving SOC with chemotherapy followed by niraparib maintenance. This comparison will be investigated in participants of newly diagnosed stage III or IV advanced non-mucinous epithelial ovarian cancer participants and also to compare PFS of all participants with Stage III or IV high-grade non-mucinous epithelial ovarian cancer treated with platinum-based combination therapy, dostarlimab (TSR-042), and niraparib to SOC platinum-based combination therapy. The currently recommended SOC therapy for the first line treatment of Stage III or IV ovarian cancer is the combination of paclitaxel and carboplatin, with or without concurrent and maintenance bevacizumab. Participants will receive SOC during the chemotherapy Run-In period (cycle 1) before randomization to study treatment (cycle 2). Concurrent bevacizumab use must be determined prior to randomization at cycle 2.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2018
Longer than P75 for phase_3
181 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 28, 2018
CompletedFirst Posted
Study publicly available on registry
July 27, 2018
CompletedStudy Start
First participant enrolled
October 11, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2024
CompletedResults Posted
Study results publicly available
December 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2029
ExpectedDecember 31, 2025
December 1, 2025
6.1 years
June 28, 2018
October 29, 2025
December 9, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
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).
Up to approximately 316 weeks
Secondary Outcomes (12)
Overall Survival (OS)
Up to approximately 316 weeks
PFS Determined by Blinded Independent Central Review (BICR) Per RECIST v1.1 Criteria
Up to approximately 316 weeks
Time to First Subsequent Therapy (TFST)
Up to approximately 316 weeks
Time to Second Subsequent Therapy (TSST)
Up to approximately 316 weeks
Time to Second Progression (PFS2)
Up to approximately 316 weeks
- +7 more secondary outcomes
Study Arms (3)
Participants receiving SOC+placebo
PLACEBO COMPARATORParticipants 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 COMPARATORParticipants 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
EXPERIMENTALParticipants 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
Interventions
Participants will receive oral capsules of niraparib as a unit dosage strength of 100 milligrams (mg)
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
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.
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
Participants will receive oral capsules of niraparib-placebo as a unit dosage strength of 100 mg.
Eligibility Criteria
You may qualify if:
- 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, endometrioid, clear cell, carcinosarcoma, and mixed pathologies), fallopian tube, or peritoneal cancer that is Stage III or IV according to the International Federation of Gynecology and Obstetrics (FIGO) or tumor, node and metastasis staging criteria.
- All participants with Stage IV disease are eligible. This includes those with inoperable disease, those who undergo primary debulking surgery (PDS) (R0 or macroscopic disease), or those for whom neoadjuvant chemotherapy (NACT) is planned.
- Participants with Stage III are eligible if they meet protocol defined criteria.
- Participants must provide a blood sample for circulating tumor deoxyribonucleic acid (ctDNA) homologous recombinant repair (HRR) testing at pre-screening or screening.
- Participant must provide a minimum of 1 formalin-fixed paraffin embedded (FFPE) block slide at pre-screening or screening for PD-L1, homologous recombinant deficiency (HRD) testing.
- Participants of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin) within 3 days prior to receiving the first dose of study treatment.
- Participants must be postmenopausal, free from menses for \>1 year, surgically sterilized, or willing to use highly effective contraception to prevent pregnancy or must agree to abstain from activities that could result in pregnancy throughout the study, starting with enrollment through 180 days after the last dose of study treatment.
- Participants must have adequate organ function: Absolute neutrophil count (ANC) \>=1500/micro liter (μL;) Platelet count \>=100000/μL; Hemoglobin \>=9 grams per deciliter (g/dL); Serum creatinine \<=1.5 × upper limit of normal (ULN) or calculated creatinine clearance \>=60 milliliters per minute (mL/min) using the Cockcroft-Gault equation; total bilirubin \<=1.5 × ULN or direct bilirubin \<=1.5 × ULN; AST and ALT \<=2.5 × ULN unless liver metastases are present, in which case they must be \<=5 × ULN.
- Participants must have an ECOG score of 0 or 1.
- Participants must have normal blood pressure (BP) or adequately treated and controlled hypertension (systolic BP \<=140 millimeters of mercury (mmHg) and/or diastolic BP \<=90 mmHg).
- Participants must agree to complete health related quality of life (HRQoL) questionnaires throughout the study.
- Participants must be able to take oral medication.
You may not qualify if:
- Participant has mucinous, germ cell, transitional cell, or undifferentiated tumor.
- Participant has low-grade or Grade 1 epithelial ovarian cancer.
- Participant has not adequately recovered from prior major surgery.
- Participant is pregnant or is expecting to conceive children while receiving study drug or for up to 180 days after the last dose of study drug. Participant is breastfeeding or is expecting to breastfeed within 30 days of receiving the final dose of study drug (women should not breastfeed or store breastmilk for use, during niraparib treatment and for 30 days after receiving the final dose of study treatment).
- Participant has known active central nervous system metastases, carcinomatous meningitis, or both.
- Participant has clinically significant cardiovascular disease.
- Participant has a bowel obstruction by clinical symptoms or computed tomography (CT) scan, subocclusive mesenteric disease, abdominal or gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess.
- Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Participant has been diagnosed and/or treated with any therapy for invasive cancer \<5 years from study enrollment, completed adjuvant chemotherapy and/or targeted therapy (example, trastuzumab) less than 3 years from enrollment, or completed adjuvant hormonal therapy less than 4 weeks from enrollment.
- Participants with definitively treated non-invasive malignancies such as cervical carcinoma in situ, ductal carcinoma in situ, Grade 1 or 2, Stage I endometrial cancer, or non-melanomatous skin cancer are allowed.
- Participant is at increased bleeding risk due to concurrent conditions (example, major injuries or major surgery within the past 28 days prior to start of study treatment and/or history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
- Participant is immunocompromised.
- Participant has known active hepatitis B (example, hepatitis B surface antigen reactive) or hepatitis C (example, hepatitis C virus ribonucleic acid \[qualitative\] is detected).
- Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or uncontrolled infection.
- Participant has had investigational therapy administered within 4 weeks or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (182)
GSK Investigational Site
Anchorage, Alaska, 99508, United States
GSK Investigational Site
Phoenix, Arizona, 85016, United States
GSK Investigational Site
Tucson, Arizona, 85711, United States
GSK Investigational Site
Los Angeles, California, 90027, United States
GSK Investigational Site
Los Angeles, California, 90048, United States
GSK Investigational Site
Newport Beach, California, 92663, United States
GSK Investigational Site
Farmington, Connecticut, 06030, United States
GSK Investigational Site
Hartford, Connecticut, 06102, United States
GSK Investigational Site
Gainesville, Florida, 32608, United States
GSK Investigational Site
Jacksonville, Florida, 32256, United States
GSK Investigational Site
Geneva, Illinois, 60555, United States
GSK Investigational Site
Warrenville, Illinois, 60555, United States
GSK Investigational Site
Zion, Illinois, 60099, United States
GSK Investigational Site
Covington, Louisiana, 70433, United States
GSK Investigational Site
New Orleans, Louisiana, 70121, United States
GSK Investigational Site
Shreveport, Louisiana, 71103, United States
GSK Investigational Site
Scarborough, Maine, 04074, United States
GSK Investigational Site
Baltimore, Maryland, 21201, United States
GSK Investigational Site
Silver Spring, Maryland, 20910, United States
GSK Investigational Site
Boston, Massachusetts, 02215, United States
GSK Investigational Site
Springfield, Massachusetts, 01199, United States
GSK Investigational Site
Worcester, Massachusetts, 01605, United States
GSK Investigational Site
Minneapolis, Minnesota, 55404, United States
GSK Investigational Site
Minneapolis, Minnesota, 55455, United States
GSK Investigational Site
Billings, Montana, 59101, United States
GSK Investigational Site
Neptune City, New Jersey, 07753, United States
GSK Investigational Site
Teaneck, New Jersey, 07666, United States
GSK Investigational Site
Hawthorne, New York, 10532, United States
GSK Investigational Site
New York, New York, 10016, United States
GSK Investigational Site
New York, New York, 10029, United States
GSK Investigational Site
New York, New York, 10065, United States
GSK Investigational Site
Rochester, New York, 14620-4159, United States
GSK Investigational Site
Stony Brook, New York, 11794, United States
GSK Investigational Site
Syracuse, New York, 13210, United States
GSK Investigational Site
Charlotte, North Carolina, 28204, United States
GSK Investigational Site
Canton, Ohio, 44710, United States
GSK Investigational Site
Cincinnati, Ohio, 45219, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73104, United States
GSK Investigational Site
Eugene, Oregon, 97401, United States
GSK Investigational Site
Portland, Oregon, 97227, United States
GSK Investigational Site
Paoli, Pennsylvania, 19301, United States
GSK Investigational Site
Philadelphia, Pennsylvania, 19111, United States
GSK Investigational Site
Pittsburgh, Pennsylvania, 15224, United States
GSK Investigational Site
Pittsburgh, Pennsylvania, 15232, United States
GSK Investigational Site
Willow Grove, Pennsylvania, 19001-3788, United States
GSK Investigational Site
Wynnewood, Pennsylvania, 19096, United States
GSK Investigational Site
Providence, Rhode Island, 02905, United States
GSK Investigational Site
Charleston, South Carolina, 29425, United States
GSK Investigational Site
Sioux Falls, South Dakota, 57105, United States
GSK Investigational Site
Knoxville, Tennessee, 37920, United States
GSK Investigational Site
Nashville, Tennessee, 37203, United States
GSK Investigational Site
Nashville, Tennessee, 37205, United States
GSK Investigational Site
Austin, Texas, 78731, United States
GSK Investigational Site
Dallas, Texas, 75246, United States
GSK Investigational Site
Fort Worth, Texas, 76104, United States
GSK Investigational Site
Houston, Texas, 77030, United States
GSK Investigational Site
San Antonio, Texas, 78240, United States
GSK Investigational Site
The Woodlands, Texas, 77380, United States
GSK Investigational Site
Tyler, Texas, 75702, United States
GSK Investigational Site
Ogden, Utah, 84405, United States
GSK Investigational Site
Charlottesville, Virginia, 22903, United States
GSK Investigational Site
Norfolk, Virginia, 23502, United States
GSK Investigational Site
Kennewick, Washington, 99336, United States
GSK Investigational Site
Seattle, Washington, 98104, United States
GSK Investigational Site
Seattle, Washington, 98109, United States
GSK Investigational Site
Minsk, 223040, Belarus
GSK Investigational Site
Brasschaat, 2930, Belgium
GSK Investigational Site
Bruges, 8000, Belgium
GSK Investigational Site
Vancouver, British Columbia, V5Z 4E6, Canada
GSK Investigational Site
London, Ontario, N6A 4L6, Canada
GSK Investigational Site
Toronto, Ontario, M4N 3M5, Canada
GSK Investigational Site
Montreal, Quebec, H2X 3E4, Canada
GSK Investigational Site
Montreal, Quebec, H4A 3J1, Canada
GSK Investigational Site
Sherbrooke, Quebec, J1H 5N4, Canada
GSK Investigational Site
Windsor, 1000, Canada
GSK Investigational Site
Prague, 128 51, Czechia
GSK Investigational Site
Prague, 180 81, Czechia
GSK Investigational Site
Copenhagen, DK- 2100, Denmark
GSK Investigational Site
Herlev, 2730, Denmark
GSK Investigational Site
Roskilde, 4000, Denmark
GSK Investigational Site
Helsinki, 00029, Finland
GSK Investigational Site
Kuopio, 70210, Finland
GSK Investigational Site
Tampere, 33520, Finland
GSK Investigational Site
Turku, 20520, Finland
GSK Investigational Site
Angers, 49055, France
GSK Investigational Site
Avignon, 84918, France
GSK Investigational Site
Besançon, 25030, France
GSK Investigational Site
Bordeaux, 33000, France
GSK Investigational Site
Bron, 69495, France
GSK Investigational Site
Caen, 14000, France
GSK Investigational Site
Cholet, 69373, France
GSK Investigational Site
Clermont-Ferrand, 63011, France
GSK Investigational Site
Dijon, 21079, France
GSK Investigational Site
Grenoble, 38000, France
GSK Investigational Site
Grenoble, 38700, France
GSK Investigational Site
Le Mans, 72000, France
GSK Investigational Site
Lille, 59000, France
GSK Investigational Site
Lyon, 69008, France
GSK Investigational Site
Lyon, 69373, France
GSK Investigational Site
Lyon, 69495, France
GSK Investigational Site
Marseille, 13273, France
GSK Investigational Site
Montpellier, 34070, France
GSK Investigational Site
Montpellier, 34298, France
GSK Investigational Site
Nancy, 54100, France
GSK Investigational Site
Nantes, 44227, France
GSK Investigational Site
Nice, 06189, France
GSK Investigational Site
Nîmes, 30029, France
GSK Investigational Site
Paris, 75014, France
GSK Investigational Site
Paris, 75020, France
GSK Investigational Site
Paris, 75248, France
GSK Investigational Site
Paris, 75908, France
GSK Investigational Site
Paris, 75970, France
GSK Investigational Site
Pierre-Bénite, 69495, France
GSK Investigational Site
Plerin-sur-mer, 22190, France
GSK Investigational Site
Poitiers, 86021, France
GSK Investigational Site
Reims, 51056, France
GSK Investigational Site
Rennes, 35042, France
GSK Investigational Site
Saint-Cloud, 75248, France
GSK Investigational Site
Saint-Priest-en-Jarez, 42271, France
GSK Investigational Site
Strasbourg, 67091, France
GSK Investigational Site
Toulouse, 31059, France
GSK Investigational Site
Tours, 37044, France
GSK Investigational Site
Villejuif, 94805, France
GSK Investigational Site
Berlin, 13125, Germany
GSK Investigational Site
Hamburg, 22457, Germany
GSK Investigational Site
Kiel, 24103, Germany
GSK Investigational Site
Münster, 48149, Germany
GSK Investigational Site
Ravensburg, 88212, Germany
GSK Investigational Site
Wolfsburg, 38440, Germany
GSK Investigational Site
Athens, 115 28, Greece
GSK Investigational Site
Athens, 11528, Greece
GSK Investigational Site
Athens, 12462, Greece
GSK Investigational Site
Haidari - Athens, 12462, Greece
GSK Investigational Site
Marousi, 15123, Greece
GSK Investigational Site
Beersheba, 8410101, Israel
GSK Investigational Site
Haifa, 3109601, Israel
GSK Investigational Site
Haifa, 3436212, Israel
GSK Investigational Site
Holon, 5822012, Israel
GSK Investigational Site
Petah Tikva, 4941492, Israel
GSK Investigational Site
Rehovot, 76100, Israel
GSK Investigational Site
Bologna, 40138, Italy
GSK Investigational Site
Faenza, 48018, Italy
GSK Investigational Site
Lugo RA, 48018, Italy
GSK Investigational Site
Meldola FC, 47014, Italy
GSK Investigational Site
Naples, 80131, Italy
GSK Investigational Site
Amsterdam, 1081 HV, Netherlands
GSK Investigational Site
Groningen, 9700 RB, Netherlands
GSK Investigational Site
Maastricht, 6229 HX, Netherlands
GSK Investigational Site
Nijmegen, 6525 GA, Netherlands
GSK Investigational Site
Rotterdam, 3015 GD, Netherlands
GSK Investigational Site
Utrecht, 3584 CX, Netherlands
GSK Investigational Site
Kristiansand, 4632, Norway
GSK Investigational Site
Oslo, 0310, Norway
GSK Investigational Site
Tromsø, 9019, Norway
GSK Investigational Site
Olsztyn, 10-228, Poland
GSK Investigational Site
Szczecin, 70-111, Poland
GSK Investigational Site
Warsaw, 02-781, Poland
GSK Investigational Site
Bucharest, 022328, Romania
GSK Investigational Site
Cluj-Napoca, 400015, Romania
GSK Investigational Site
Cluj-Napoca, 400051, Romania
GSK Investigational Site
Constanța, 900591, Romania
GSK Investigational Site
Craiova, 200347, Romania
GSK Investigational Site
Timișoara, 300239, Romania
GSK Investigational Site
Ávila, 05071, Spain
GSK Investigational Site
Badalona, 08916, Spain
GSK Investigational Site
Barcelona, 08036, Spain
GSK Investigational Site
Girona, 17007, Spain
GSK Investigational Site
Jaén, 23007, Spain
GSK Investigational Site
Madrid, 28046, Spain
GSK Investigational Site
Madrid, 28702, Spain
GSK Investigational Site
Santiago de Compostela, 15706, Spain
GSK Investigational Site
Toledo, 45007, Spain
GSK Investigational Site
Valencia, 46010, Spain
GSK Investigational Site
Zaragoza, 50009, Spain
GSK Investigational Site
Chernihiv, 14029, Ukraine
GSK Investigational Site
Kharkiv, 61024, Ukraine
GSK Investigational Site
Lviv, 79031, Ukraine
GSK Investigational Site
Glasgow, G12 0YN, United Kingdom
GSK Investigational Site
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
GSK Investigational Site
Portsmouth, PO6 3LY, United Kingdom
GSK Investigational Site
Sutton, SM2 5PT, United Kingdom
GSK Investigational Site
Truro, TR1 3LJ, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 28, 2018
First Posted
July 27, 2018
Study Start
October 11, 2018
Primary Completion
October 31, 2024
Study Completion (Estimated)
April 30, 2029
Last Updated
December 31, 2025
Results First Posted
December 31, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will not share
GSK will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf.