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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03602859
Recruitment Status : Active, not recruiting
First Posted : July 27, 2018
Last Update Posted : January 26, 2023
Sponsor:
Collaborator:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Information provided by (Responsible Party):
Tesaro, Inc.

Study Description
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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 both in the PD-L1 positive and overall population 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.

Condition or disease Intervention/treatment Phase
Ovarian Neoplasms Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma Drug: Niraparib Drug: Dostarlimab (TSR-042) Drug: Standard of care Drug: Dostarlimab-Placebo Drug: Niraparib-Placebo Phase 3

Study Design
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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1403 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 11, 2018
Estimated Primary Completion Date : July 21, 2023
Estimated Study Completion Date : June 22, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Participants receiving SOC+placebo
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.
 Drug: Standard of care
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.

Drug: Dostarlimab-Placebo
Participants will receive 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

Drug: Niraparib-Placebo
Participants will receive oral capsules of niraparib-placebo as a unit dosage strength of 100 mg.
Active Comparator: Participants receiving SOC+niraparib
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.
 Drug: Niraparib
Participants will receive oral capsules of niraparib as a unit dosage strength of 100 milligrams (mg).
Other Name: ZEJULA

Drug: Standard of care
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.

Drug: Dostarlimab-Placebo
Participants will receive 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
Experimental: Participants receiving SOC+dostarlimab+niraparib
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.
 Drug: Niraparib
Participants will receive oral capsules of niraparib as a unit dosage strength of 100 milligrams (mg).
Other Name: ZEJULA

Drug: Dostarlimab (TSR-042)
Participants will receive 30 minutes intravenous (IV) infusions of 1000 mg dostarlimab on Day 1 every 6 weeks.

Drug: Standard of care
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.


Outcome Measures
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Primary Outcome Measures :
  1. PFS for PD-L1 positive participants [ Time Frame: Up to 5 years ]
    To compare the PFS of PD-L1 positive participants with Stage III or IV non-mucinous epithelial ovarian cancer given first-line treatment with the combination of dostarlimab with SOC chemotherapy +/- bevacizumab followed by niraparib and dostarlimab maintenance +/- bevacizumab versus SOC chemotherapy +/- bevacizumab followed by niraparib maintenance +/- bevacizumab. PFS is defined as the time from treatment randomization to the earlier date of assessment of progression or death by any cause in the absence of progression. PFS will be evaluated by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 criteria.

  2. PFS for all participants [ Time Frame: Up to 5 years ]
    To compare the PFS of all participants with Stage III or IV high-grade nonmucinous epithelial ovarian cancer given first-line treatment with the combination of dostarlimab with SOC chemotherapy +/- bevacizumab followed by niraparib and dostarlimab maintenance +/- bevacizumab versus SOC chemotherapy +/- bevacizumab followed by niraparib maintenance +/- bevacizumab. PFS is defined as the time from treatment randomization to the earlier date of assessment of progression or death by any cause in the absence of progression. PFS will be evaluated by investigator assessment per RECIST v.1.1 criteria.


Secondary Outcome Measures :
  1. PFS by Blinded Independent Central Review (BICR) per investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) criteria for PD-L1 positive participants [ Time Frame: Up to 5 years ]
    BICR determined PFS will be assessed as per RECIST criteria.

  2. Overall Survival (OS) of PD-L1 positive participants [ Time Frame: Up to 5 years ]
    OS is defined as the date of randomization to the date of death by any cause.

  3. OS of all the participants [ Time Frame: Up to 5 years ]
    OS is defined as the date of randomization to the date of death by any cause.

  4. Number of PD-L1 positive participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 5 years ]
    TEAEs are defined as, any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

  5. Number of overall participants with TEAEs [ Time Frame: Up to 5 years ]
    TEAEs are defined as, any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

  6. Number of PD-L1 positive participants with serious adverse events (SAEs) [ Time Frame: Up to 5 years ]
    SAEs are any adverse event that may result in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital abnormality or birth defect, is an important medical event.

  7. Number of overall participants with SAEs [ Time Frame: Up to 5 years ]
    SAEs are any adverse event that may result in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital abnormality or birth defect, is an important medical event.

  8. Number of PD-L1 positive participants with treatment discontinuations or dose delays or dose reductions due to adverse events [ Time Frame: Up to 5 years ]
    Adverse events are any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment.

  9. Number of overall participants with treatment discontinuations or dose delays or dose reductions due to adverse events [ Time Frame: Up to 5 years ]
    Adverse events are any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment.

  10. Number of PD-L1 positive participants with immune-related adverse events (irAEs) [ Time Frame: Up to 5 years ]
    Following events are categorized as irAEs: Diarrhea/colitis, aspartate aminotransferase (AST) or alanine aminotransferase (ALT; >3 and <=5 X upper limit of normal [ULN]), or increased bilirubin, type 1 diabetes mellitus (T1DM) or hyperglycemia, immune-related encephalitis, uveitis, myositis, hypophysitis, adrenal insufficiency, hypo- and hyperthyroidism, infusion-related reaction, pneumonitis, immune-related rash, renal failure or nephritis and recurrence of adverse events after resolution to Grade <=1.

  11. Number of overall participants with irAEs [ Time Frame: Up to 5 years ]
    Following events are categorized as irAEs: Diarrhea/colitis, AST or ALT (>3 and <=5 X ULN), or increased bilirubin, T1DM or hyperglycemia, immune-related encephalitis, uveitis, myositis, hypophysitis, adrenal insufficiency, hypo- and hyperthyroidism, infusion-related reaction, pneumonitis, immune-related rash, renal failure or nephritis and recurrence of AEs after resolution to Grade <=1.

  12. Number of PD-L1 positive participants with changes in Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Up to 5 years ]
    Performance status will be assessed using the ECOG performance status scale: ranging from Grade 0 to 5, Grade 0 denoting fully active and Grade 5 denoting death.

  13. Number of overall participants with changes in ECOG performance status [ Time Frame: Up to 5 years ]
    Performance status will be assessed using the ECOG performance status scale: ranging from Grade 0 to 5, Grade 0 denoting fully active and Grade 5 denoting death.

  14. Number of PD-L1 positive participants with abnormal hematology results [ Time Frame: Up to 5 years ]
    Blood samples will be collected for the analysis of hematologic parameters including: hemoglobin, platelet count, white blood cell count, differential white blood cell count, coagulation factors-International normalized ratio (INR) and activated partial thromboplastin time.

  15. Number of all the participants with abnormal hematology results [ Time Frame: Up to 5 years ]
    Blood samples will be collected for the analysis of hematologic parameters including: hemoglobin, platelet count, white blood cell count, differential white blood cell count, coagulation factors-INR and activated partial thromboplastin time.

  16. Number of PD-L1 positive participants with abnormal clinical chemistry results [ Time Frame: Up to 5 years ]
    Blood samples will be collected for the analysis of clinical chemistry parameters including: amylase, thyroid function (thyroid stimulating hormone [TSH]), urea or blood urea nitrogen, creatinine, albumin, total protein, ALT, AST, total bilirubin, Glucose, Magnesium, Calcium, Chloride, Potassium and Sodium.

  17. Number of all the participants with abnormal clinical chemistry results [ Time Frame: Up to 5 years ]
    Blood samples will be collected for the analysis of clinical chemistry parameters including: amylase, thyroid function (TSH), urea or blood urea nitrogen, creatinine, albumin, total protein, ALT, AST, total bilirubin, Glucose, Magnesium, Calcium, Chloride, Potassium and Sodium.

  18. Change from Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) assessment among PD-L1 positive participants [ Time Frame: Baseline and up to 5 years ]
    EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases. EQ-5D-5L consists of a descriptive section of 5 questions/dimensions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is measured by 5-point Likert scale (no problems, slight problems, moderate problems, severe problems and extreme problems).

  19. Change from Baseline in the EQ-5D-5L assessment among all participants [ Time Frame: Baseline and up to 5 years ]
    EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases. EQ-5D-5L consists of a descriptive section of 5 questions/dimensions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is measured by 5-point Likert scale (no problems, slight problems, moderate problems, severe problems and extreme problems).

  20. Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) assessment among PD-L1 positive participants [ Time Frame: Baseline and Up to 5 years ]
    EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in participants with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/quality of life scale (GHS/QOL), and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). Response options are 1 to 4. Higher score indicates better health-related quality of life.

  21. Change from Baseline in the EORTC-QLQ-C30 assessment among all the participants [ Time Frame: Baseline and up to 5 years ]
    EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in participants with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a GHS/QOL, and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Response options are 1 to 4. Higher score indicates better health-related quality of life.

  22. Change from Baseline in the EORTC-QLQ Ovarian Cancer Module OV28 (EORTC-QLQ-OV28) assessment among PD-L1 positive participants [ Time Frame: Baseline and up to 5 years ]
    EORTC QLQ-OV28 is a validated questionnaire to assess the overall health-related quality of life in participants with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/ gastrointestinal (GI) symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste. All questions are rated on a 4 point verbal rating scale: "Not at all," "A little," "Quite a bit," and "Very much."

  23. Change from Baseline in the EORTC-QLQ-OV28 assessment among all the participants [ Time Frame: Baseline and up to 5 years ]
    EORTC QLQ-OV28 is a validated questionnaire to assess the overall health-related quality of life in all the participants with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/GI symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste. All questions are rated on a 4 point verbal rating scale: "Not at all," "A little," "Quite a bit," and "Very much."

  24. Time to symptom worsening in the EQ-5D-5L assessment among the PD-L1 positive participants [ Time Frame: Up to 5 years ]
    EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases. EQ-5D-5L consists of a descriptive section of 5 questions/dimensions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is measured by 5-point Likert scale (no problems, slight problems, moderate problems, severe problems and extreme problems).

  25. Time to symptom worsening in the EQ-5D-5L assessment among all the participants [ Time Frame: Up to 5 years ]
    EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases. EQ-5D-5L consists of a descriptive section of 5 questions/dimensions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is measured by 5-point Likert scale (no problems, slight problems, moderate problems, severe problems and extreme problems).

  26. Time to symptom worsening in the EORTC-QLQ-C30 assessment among the PD-L1 positive participants [ Time Frame: Up to 5 years ]
    EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in participants with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a GHS/QOL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Response options are 1 to 4. Higher score indicates better health-related quality of life.

  27. Time to symptom worsening in the EORTC QLQ-C30 assessment among all the participants [ Time Frame: Up to 5 years ]
    EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in participants with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a GHS/QOL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Response options are 1 to 4. Higher score indicates better health-related quality of life.

  28. Time to symptom worsening in the EORTC-QLQ-OV28 assessment among the PD-L1 positive participants [ Time Frame: Up to 5 years ]
    EORTC QLQ-OV28 is a validated questionnaire to assess the overall he PFS2, health-related quality of life in participants with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/GI symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste. All questions are rated on a 4 point verbal rating scale: "Not at all," "A little," "Quite a bit," and "Very much."

  29. Time to symptom worsening in the EORTC-QLQ-OV28 assessment among all the participants [ Time Frame: Up to 5 years ]
    EORTC QLQ-OV28 is a validated questionnaire to assess the overall he PFS2, health-related quality of life in participants with local or advanced ovarian cancer. EORTC QLQ-OV28 consists of 28 questions evaluated across eight multi-item and 4 single item scales: abdominal/GI symptoms, peripheral neuropathy, hormonal symptoms, body image, attitude to disease/treatment, chemotherapy side effects, and sexuality, and single items scales for indigestion/heartburn, hair loss, upset due to hair loss, and taste. All questions are rated on a 4 point verbal rating scale: "Not at all," "A little," "Quite a bit," and "Very much."

  30. Time to first subsequent therapy (TFST) in PD-L1 positive participants [ Time Frame: Up to 5 years ]
    TFST is defined as the time from randomization until the start date of the first subsequent anti-cancer therapy or death, whichever occurs first.

  31. TFST in all the participants [ Time Frame: Up to 5 years ]
    TFST is defined as the time from randomization until the start date of the first subsequent anti-cancer therapy or death, whichever occurs first.

  32. Time to second subsequent therapy (TSST) in PD-L1 positive participants [ Time Frame: Up to 5 years ]
    TSST is defined as the time from randomization until the start date of the second subsequent anti-cancer therapy or death, whichever occurs first.

  33. TSST in all the participants [ Time Frame: Up to 5 years ]
    TSST is defined as the time from randomization until the start date of the second subsequent anti-cancer therapy or death, whichever occurs first.

  34. Time to progression on next-line therapy (PFS2,) in PD-L1 positive participants [ Time Frame: Up to 5 years ]
    PFS2 is defined as the time from randomization until PD per investigator's assessment after starting follow-up anti-cancer therapy or death due to any cause, whichever occurs first.

  35. PFS2 in all the participants [ Time Frame: Up to 5 years ]
    PFS2 is defined as the time from randomization until PD per investigator's assessment after starting follow-up anti-cancer therapy or death due to any cause, whichever occurs first.

  36. Objective Response Rate (ORR) among PD-L1 positive participants [ Time Frame: Up to 5 years ]
    ORR, defined as the percentage of participants with complete response (CR) or partial response (PR) on study treatment as assessed by RECIST v.1.1 criteria for participants with measurable disease.

  37. ORR among all the participants [ Time Frame: Up to 5 years ]
    ORR, defined as the percentage of participants with complete response (CR) or partial response (PR) on study treatment as assessed by RECIST v.1.1 criteria for participants with measurable disease.

  38. Pathologic complete response (pCR) rate among PD-L1 positive participants [ Time Frame: Up to 5 years ]
    pCR rate, per investigator assessment, defined as the rate of pathologic complete responseas assessed by the evaluation of residual microscopic disease at the time of surgery in neoadjuvant participants.

  39. pCR rate among all the participants [ Time Frame: Up to 5 years ]
    pCR rate, per investigator assessment, defined as the rate of pathologic complete responseas assessed by the evaluation of residual microscopic disease at the time of surgery in neoadjuvant participants.

  40. Duration of response (DOR) in PD-L1 positive participants [ Time Frame: Up to 5 years ]
    DOR, defined as the time from first documentation of CR or PR until the time of first documentation of PD as assessed by RECIST v.1.1, or death by any cause in the absence of progression, whichever occurs first.

  41. DOR in all the participants [ Time Frame: Up to 5 years ]
    DOR, defined as the time from first documentation of CR or PR until the time of first documentation of PD as assessed by RECIST v.1.1, or death by any cause in the absence of progression, whichever occurs first.

  42. Disease control rate (DCR) in PD-L1 positive participants [ Time Frame: Up to 5 years ]
    DCR, defined as the proportion of participants with a best overall response of CR, PR, or stable disease (SD), as assessed by RECIST v.1.1 criteria.

  43. DCR in all the participants [ Time Frame: Up to 5 years ]
    DCR, defined as the proportion of participants with a best overall response of CR, PR, or SD, as assessed by RECIST v.1.1 criteria.

  44. Maintenance progression-free survival (MPFS) in PD-L1 positive participants [ Time Frame: Up to 5 years ]
    MPFS, defined as the time from the date of the first maintenance period dose to the date of first documentation of progression or death by any cause in the absence of progression, whichever occurs first, as determined by the investigator. Progression will be assessed by RECIST v.1.1 criteria.

  45. MPFS in all the participants [ Time Frame: Up to 5 years ]
    MPFS, defined as the time from the date of the first maintenance period dose to the date of first documentation of progression or death by any cause in the absence of progression, whichever occurs first, as determined by the investigator. Progression will be assessed by RECIST v.1.1 criteria.

  46. Plasma concentration of dostarlimab in PD-L1 positive participants [ Time Frame: Up to 5 years ]
    Blood samples will be collected for pharmacokinetic analysis of dostarlimab.

  47. Plasma concentration of dostarlimab in all the participants [ Time Frame: Up to 5 years ]
    Blood samples will be collected for pharmacokinetic analysis of dostarlimab.

  48. Number of participants with positive antidrug antibodies (ADAs) against dostarlimab in PD-L1 positive participants [ Time Frame: Up to 5 years ]
    Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.

  49. Number of participants with positive ADAs against dostarlimab in all the participants [ Time Frame: Up to 5 years ]
    Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays.

  50. Plasma concentration of niraparib in PD-L1 positive participants [ Time Frame: Up to 5 years ]
    Blood samples will be collected for pharmacokinetic analysis of niraparib.

  51. Plasma concentration of niraparib in all the participants [ Time Frame: Up to 5 years ]
    Blood samples will be collected for pharmacokinetic analysis of niraparib.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female participants will be included in the study.
Accepts Healthy Volunteers:   No
Criteria

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, 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.

Exclusion Criteria:

  • 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.
  • Participant has received a live vaccine within 14 days of planned start of study therapy. Seasonal influenza vaccines that do not contain live viruses are allowed.
  • Participant has a known contraindication or uncontrolled hypersensitivity to the components of paclitaxel, carboplatin, niraparib, bevacizumab, dostarlimab, or their excipients.
  • Prior treatment for high-grade nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer (immunotherapy, anti-cancer therapy, radiation therapy).
  • Participant has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic therapy (example, thyroid hormone or insulin).
  • Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03602859


Locations
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Sponsors and Collaborators
Tesaro, Inc.
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT03602859    
Other Study ID Numbers: 213350
3000-03-005 ( Other Identifier: Tesaro )
First Posted: July 27, 2018    Key Record Dates
Last Update Posted: January 26, 2023
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tesaro, Inc.:
FIRST
FIRST trial
Niraparib
Dostarlimab (TSR-042)
Ovarian cancer
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
 Genital Diseases
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Niraparib
Dostarlimab
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents