Ovarian NeoplasmsPhase 2MOONSTONENCT03955471
Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Participants With Platinum Resistant Ovarian Cancer
A Phase 2 study testing Niraparib and Dostarlimab in people with Ovarian Neoplasms, run by Tesaro, Inc. at 27 sites in United States.
Trial summary
This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and dostarlimab (TSR-042) in participants with advanced, relapsed, high-grade ovarian, fallopian tube, endometrioid, clear cell ovarian or primary peritoneal cancer without known breast cancer susceptibility… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Neoplasms
- What is being tested?
- Niraparib and Dostarlimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 27 sitesUnited States
- Study dates
- 3 Oct 2019to 12 Jan 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be female >=18 years of age, able to understand the study procedures, and subsequently agreed to participate in the study by providing written informed consent.
- Participants must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer.
- Participants must be considered resistant to the last administered platinum therapy.
- Participants must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer.
- Participants must have been previously treated with platinum-based regimen, taxane agent(s), and bevacizumab.
- Participant has measurable disease according to RECIST v.1.1.
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- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participant has adequate organ function.
- Females with childbearing potential have a serum pregnancy test that is negative 72 prior first dose and are not breastfeeding. Participant must also agree to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment.
- Participant must provide formalin fixed paraffin embedded (FFPE) tumor tissue block(s) with sufficient tumor content (as confirmed by the Sponsor's designated central laboratory) during screening to enable BRCA testing and PD-L1 testing. The use of slides created from paraffin-embedded tissue as opposed to FFPE blocks must be approved by the Sponsor.
- Participant must agree to complete health-related quality of life (HRQoL) questionnaires throughout the study.
Who cannot join
- Participant who experienced disease progression within 3 months (12 weeks or 84 days) of first-line platinum therapy.
- Participants with a known deleterious or suspected BRCA 1 or 2 mutation.
- Participant has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
- Participant has received prior therapy with a PARP-1/PARP-2 inhibitor.
- Participant has a known hypersensitivity to dostarlimab (TSR-042), Niraparib, their components, or their excipients.
- Participant has a known history of myelodysplastic syndrome or acute myeloid leukemia.
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- Participant has not recovered from prior chemotherapy induced adverse events.
- Participant has a known diagnosis of immunodeficiency or is receiving systemic steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Participant is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment.
- Participant has received prior systemic anticancer therapy including cytotoxic chemotherapy, hormonal therapy given with the intention to treat ovarian cancer, or biological therapy within 3 weeks of the first dose of study treatment.
- Participant has received live vaccine within 14 days of planned start of study therapy
- Participant has symptomatic uncontrolled brain or leptomeningeal metastases. (If investigator feels participant symptoms are not symptomatic, participants can undergo a scan to confirm for eligibility).
- Participant had major surgery with 4 weeks of starting the first dose of the study treatment or participant has not recovered from any effects of any major surgery.
- Participant has a known additional malignancy that progressed or required active treatment within the last 2 years.
- Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active controlled infection.
- Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
- Participant has known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus ribonucleic acid, qualitative).
- Participant with a known history of human immunodeficiency virus (HIV) are allowed if they meet all of the following criteria:
- Cluster of differentiation 4 >=350/microliter (μL) and viral load <400 copies/milliliter (mL)
- No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment
- No history of HIV-associated malignancy for the past 5 years
- Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV started >4 weeks prior to study enrollment
- Participant is immunocompromised. Participants with splenectomy are allowed.
- Participant has an ongoing bowel obstruction or has other conditions that would lead to impaired absorption of oral niraparib.
- Participant has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
United States27 sites
GSK Investigational Site
Austin, Texas, 78731
GSK Investigational Site
Boston, Massachusetts, 02114
GSK Investigational Site
Boston, Massachusetts, 02215
GSK Investigational Site
Burlington, Massachusetts, 01805
GSK Investigational Site
Charlottesville, Virginia, 22903
GSK Investigational Site
Chattanooga, Tennessee, 37403
GSK Investigational Site
Cleveland, Ohio, 44106
GSK Investigational Site
Cleveland, Ohio, 44124
GSK Investigational Site
Deerfield Beach, Florida, 33442
GSK Investigational Site
Duarte, California, 91010
GSK Investigational Site
Durham, North Carolina, 27710
GSK Investigational Site
Eugene, Oregon, 97401
GSK Investigational Site
Fort Worth, Texas, 76104
GSK Investigational Site
Germantown, Tennessee, 38138
GSK Investigational Site
Iowa City, Iowa, 52242-1009
GSK Investigational Site
Jackson, Mississippi, 39216
GSK Investigational Site
Miami, Florida, 33136
GSK Investigational Site
Minneapolis, Minnesota, 55404
GSK Investigational Site
New York, New York, 10022
GSK Investigational Site
Newport Beach, California, 92663
GSK Investigational Site
Orange, California, 92868
GSK Investigational Site
Orlando, Florida, 32804
GSK Investigational Site
Providence, Rhode Island, 02905
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
Scottsdale, Arizona, 85258
GSK Investigational Site
Solvang, California, 93463
GSK Investigational Site
Tampa, Florida, 33612
About this study
Official title: A Phase 2 Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Patients With Platinum-Resistant Ovarian Cancer (MOONSTONE)
This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and dostarlimab (TSR-042) in participants with advanced, relapsed, high-grade ovarian, fallopian tube, endometrioid, clear cell ovarian or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease and who have also been previously treated with bevacizumab.
- Conditions
- Ovarian Neoplasms
- Being tested
- Niraparib, Dostarlimab
- Keywords
- Open-label, Single-arm, Efficacy and Safety, Platinum-resistant ovarian cancer, Niraparib, dostarlimab
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called ZEJULA
Niraparib is a potent, orally active poly (adenosine diphosphate-ribose) polymerase (PARP)-1 and PARP2 inhibitor being developed as a treatment for participants with tumors that harbor defects in the homologous recombination deoxyribonucleic acid (DNA) repair pathway or that are driven by PARP-mediated transcription factors.
DostarlimabDrug
TSR-042 is a humanized monoclonal antibody that binds with high affinity to programmed cell death-1 (PD-1) resulting in inhibition of binding to programmed cell-death receptor ligands 1 and 2 (PD-L1 and PD-L2).
| Study group | Role | What they receive |
|---|---|---|
| Niraparib+Dostarlimab (TSR-042) | Experimental | Participants with body weight ≥77 kilogram (kg) and platelet count ≥150,000/microliter (μL) at baseline were administered Niraparib 300 milligram (mg) once daily (QD) and participants with body weight <77 kg or platelet count <150,000/μL at baseline were administered Niraparib 200 mg QD. Niraparib was administered continuously until Progressive disease (PD) or toxicity. Dostarlimab (TSR-042) was administered as an intravenous (IV) infusion of 500 mg once every three weeks (Q3W) from Cycle 1 Day 1 through Cycle 4. Beginning at Cycle 5, Dostarlimab (TSR-042) was administered via an IV infusion of 1000 mg on Day 1 of each 6-week cycle until PD or toxicity, up to 27 months. Receives: Drug: Niraparib; Drug: Dostarlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC)
ORR is defined as the percentage of participants who have achieved confirmed complete response (CR) or partial response (PR), as determined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria based on Investigator assessment and computed tomography (CT) scans were commonly used for tumor imaging.
Measured: Up to approximately 22 months
ORR in Participants With PROC Who Have Programmed Cell Death-ligand 1 (PD-L 1) Positive Status
ORR is defined as the percentage of participants who have achieved confirmed CR or PR, as determined by RECIST v1.1 criteria based on Investigator assessment and CT scans were commonly used for tumor imaging. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with combined positive score (vCPS) >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Measured: Up to approximately 22 months
Secondary outcomes (25)
Duration of Response (DOR) in Participants With PROC
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment.
Measured: Up to approximately 22 months
DOR in Participants With PROC Who Have PD-L 1 Positive Status
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Measured: Up to approximately 22 months
Progression-free Survival (PFS) in Participants With PROC
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment.
Measured: Up to approximately 22 months
PFS in Participants With PROC Who Have PD-L 1 Positive Status
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Measured: Up to approximately 22 months
Overall Survival (OS) in Participants With PROC
OS is defined as the time from the date of the first dose of study treatment to the date of death by any cause.
Measured: Up to approximately 22 months
OS in Participants With PROC Who Have PD-L 1 Positive Status
OS is defined as the time from the date of the first dose of study treatment to the date of death by any cause. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Measured: Up to approximately 22 months
Disease Control Rate (DCR) in Participants With PROC
DCR is defined as the percentage of participants who have achieved best overall response (BOR) of CR, PR, or stable disease (SD) per RECIST v.1.1 based on the investigator's assessment.
Measured: Up to approximately 22 months
DCR in Participants With PROC Who Have PD-L 1 Positive Status
DCR is defined as the percentage of participants who have achieved BOR of CR, PR, or SD per RECIST v.1.1 based on the investigator's assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Measured: Up to approximately 22 months
ORR in Participants With PROC Based on Independent Review Committee (IRC) Assessment
ORR is defined as the percentage of participants who have achieved confirmed CR or PR per RECIST v1.1 based on the independent review committee assessment.
Measured: Up to approximately 22 months
ORR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
ORR is defined as the percentage of participants who have achieved confirmed CR or PR per RECIST v1.1 based on the independent review committee assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Measured: Up to approximately 22 months
DOR in Participants With PROC Based on IRC Assessment
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Independent Review Committee assessment.
Measured: Up to approximately 22 months
DOR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Independent Review Committee assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Measured: Up to approximately 22 months
PFS in Participants With PROC Based on IRC Assessment
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on Independent Review Committee Assessment.
Measured: Up to approximately 22 months
PFS in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on IRC Assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Measured: Up to approximately 22 months
DCR in Participants With PROC Based on IRC Assessment
DCR is defined as the percentage of participants who have achieved BOR of CR, PR, or SD per RECIST v.1.1 based on IRC Assessment.
Measured: Up to approximately 22 months
DCR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
DCR is defined as the percentage of participants who have achieved BOR of CR, PR, or SD per RECIST v.1.1 based on Independent Review Committee Assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Measured: Up to approximately 22 months
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs) and Adverse Event of Special Interest (AESI)
An AE is any untoward medical occurrence in a patient administered with a medicinal product and that does which may or may not have a causal relationship with this treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. TEAEs are any event that occurred between first dose of study drug up to 22 months, which were absent before treatment or that had worsened relative to pretreatment state. AESI were any AE (serious or non-serious) that is of scientific and medical concern specific to the study treatment, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was done.
Measured: Up to approximately 27 months
Number of Participants With Grade Shift From Baseline in Hematology
Blood samples were collected for the analysis of hematology parameters and each parameter was graded according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.3. Grade 0: Normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent measurement prior to the first administration of study treatment. Data has been presented for the number of participants with hematology grade shifts from baseline grade to grade 3 and 4 for each parameter.
Measured: Up to approximately 27 months
Number of Participants With Grade Shift From Baseline in Plasma Chemistry
Blood samples were collected and the clinical chemistry parameters assessed were Albumin (Alb), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), sodium, total bilirubin (TB), creatinine, glucose, magnesium and potassium. The Grade shift post baseline data of each parameter from Grade 0 through Grade 4 was based on the CTCAE version 4.03, grading scale, as per intensity, namely Grade 0: Normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent measurement prior to the first administration of study treatment. Data has been presented for the number of participants with plasma chemistry grade shifts from baseline grade to grade 3 and 4 for each parameter.
Measured: Up to approximately 27 months
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Baseline was defined as the most recent measurement prior to the first administration of study treatment. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The minimum (min) and maximum (max) change from baseline values have been reported.
Measured: Up to approximately 27 months
Change From Baseline in Pulse Rate
Baseline was defined as the most recent measurement prior to the first administration of study treatment. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The minimum (min) and maximum (max) change from baseline values have been reported.
Measured: Up to approximately 27 months
Change From Baseline in Temperature
Baseline was defined as the most recent measurement prior to the first administration of study treatment. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The minimum (min) and maximum (max) change from baseline values have been reported.
Measured: Up to approximately 27 months
Change From Baseline in Prothrombin International Normalized Ratio
Blood samples were collected to evaluate Prothrombin International Normalized Ratio (INR). Baseline was defined as the most recent measurement prior to the first administration of study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline and up to approximately 27 months
Change in Baseline in Activated Partial Thromboplastin Time
Blood samples were planned to be collected to evaluate activated partial thromboplastin time (APTT). Baseline was defined as the most recent measurement prior to the first administration of study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline and up to approximately 27 months
Change From Baseline in Thyrotropin
Blood samples were collected to evaluate thyrotropin at indicated time points. Baseline was defined as the most recent measurement prior to the first administration of study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline and up to approximately 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2019
- Study start3 Oct 2019
- Primary completion18 Aug 2021
- Study completion12 Jan 2022
Why it stopped: The study will not resume based on the results of a planned interim analysis that showed futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tesaro, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Gynecologic Oncology Group
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03955471
- Sponsor's protocol ID
- 213353
- Other IDs
- 3000-02-006
- Acronym
- MOONSTONE
- Status last verified
- Aug 2022
- First submitted
- 16 May 2019
- Last updated
- 10 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Randall LM, O'Malley DM, Monk BJ, Coleman RL, Gaillard S, Adams S, Duska LR, Dalton H, Holloway RW, Huang M, Chon HS, Cloven NG, ElNaggar AC, O'Cearbhaill RE, Waggoner S, Tarkar A, Striha A, Nelsen LM, Baines A, Samnotra V, Konstantinopoulos PA. Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032). Gynecol Oncol. 2023 Nov;178:161-169. doi: 10.1016/j.ygyno.2023.10.005. Epub 2023 Oct 25.
PubMed 37890345
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Patients With Platinum-Resistant Ovarian Cancer (MOONSTONE)
- ClinicalTrials.gov ID
- NCT03955471
- Acronym / sponsor ID
- MOONSTONE / 213353
- Conditions
- Ovarian Neoplasms
- Keywords
- Open-label, Single-arm, Efficacy and Safety, Platinum-resistant ovarian cancer, Niraparib, dostarlimab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study will not resume based on the results of a planned interim analysis that showed futility
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Tesaro, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Gynecologic Oncology Group
- Study start
- 3 Oct 2019 (actual)
- Primary completion
- 18 Aug 2021 (actual)
- Study completion
- 12 Jan 2022 (actual)
- First posted
- 20 May 2019 (actual)
- Results
- Posted 10 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and dostarlimab (TSR-042) in participants with advanced, relapsed, high-grade ovarian, fallopian tube, endometrioid, clear cell ovarian or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease and who have also been previously treated with bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Niraparib+Dostarlimab (TSR-042) | Experimental | Drug: Niraparib, Drug: DostarlimabParticipants with body weight ≥77 kilogram (kg) and platelet count ≥150,000/microliter (μL) at baseline were administered Niraparib 300 milligram (mg) once daily (QD) and participants with body weight <77 kg or platelet count <150,000/μL at baseline were administered Niraparib 200 mg QD. Niraparib was administered continuously until Progressive disease (PD) or toxicity. Dostarlimab (TSR-042) was administered as an intravenous (IV) infusion of 500 mg once every three weeks (Q3W) from Cycle 1 Day 1 through Cycle 4. Beginning at Cycle 5, Dostarlimab (TSR-042) was administered via an IV infusion of 1000 mg on Day 1 of each 6-week cycle until PD or toxicity, up to 27 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Participant must be female >=18 years of age, able to understand the study procedures, and subsequently agreed to participate in the study by providing written informed consent.
- Participants must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer.
- Participants must be considered resistant to the last administered platinum therapy.
- Participants must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer.
- Participants must have been previously treated with platinum-based regimen, taxane agent(s), and bevacizumab.
Key exclusion criteria (25 listed)
- Participant who experienced disease progression within 3 months (12 weeks or 84 days) of first-line platinum therapy.
- Participants with a known deleterious or suspected BRCA 1 or 2 mutation.
- Participant has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
- Participant has received prior therapy with a PARP-1/PARP-2 inhibitor.
- Participant has a known hypersensitivity to dostarlimab (TSR-042), Niraparib, their components, or their excipients.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: ZEJULANiraparib is a potent, orally active poly (adenosine diphosphate-ribose) polymerase (PARP)-1 and PARP2 inhibitor being developed as a treatment for participants with tumors that harbor defects in the homologous recombination deoxyribonucleic acid (DNA) repair pathway or that are driven by PARP-mediated transcription factors. | Drug | Niraparib+Dostarlimab (TSR-042) |
| DostarlimabTSR-042 is a humanized monoclonal antibody that binds with high affinity to programmed cell death-1 (PD-1) resulting in inhibition of binding to programmed cell-death receptor ligands 1 and 2 (PD-L1 and PD-L2). | Drug | Niraparib+Dostarlimab (TSR-042) |
Primary outcome
Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC)
Time frame: Up to approximately 22 months
ORR is defined as the percentage of participants who have achieved confirmed complete response (CR) or partial response (PR), as determined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria based on Investigator assessment and computed tomography (CT) scans were commonly used for tumor imaging.
ORR in Participants With PROC Who Have Programmed Cell Death-ligand 1 (PD-L 1) Positive Status
Time frame: Up to approximately 22 months
ORR is defined as the percentage of participants who have achieved confirmed CR or PR, as determined by RECIST v1.1 criteria based on Investigator assessment and CT scans were commonly used for tumor imaging. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with combined positive score (vCPS) >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
25 secondary outcomes
Duration of Response (DOR) in Participants With PROC
Time frame: Up to approximately 22 months
DOR in Participants With PROC Who Have PD-L 1 Positive Status
Time frame: Up to approximately 22 months
Progression-free Survival (PFS) in Participants With PROC
Time frame: Up to approximately 22 months
PFS in Participants With PROC Who Have PD-L 1 Positive Status
Time frame: Up to approximately 22 months
Overall Survival (OS) in Participants With PROC
Time frame: Up to approximately 22 months
OS in Participants With PROC Who Have PD-L 1 Positive Status
Time frame: Up to approximately 22 months
Disease Control Rate (DCR) in Participants With PROC
Time frame: Up to approximately 22 months
DCR in Participants With PROC Who Have PD-L 1 Positive Status
Time frame: Up to approximately 22 months
ORR in Participants With PROC Based on Independent Review Committee (IRC) Assessment
Time frame: Up to approximately 22 months
ORR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
Time frame: Up to approximately 22 months
DOR in Participants With PROC Based on IRC Assessment
Time frame: Up to approximately 22 months
DOR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
Time frame: Up to approximately 22 months
PFS in Participants With PROC Based on IRC Assessment
Time frame: Up to approximately 22 months
PFS in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
Time frame: Up to approximately 22 months
DCR in Participants With PROC Based on IRC Assessment
Time frame: Up to approximately 22 months
DCR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
Time frame: Up to approximately 22 months
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs) and Adverse Event of Special Interest (AESI)
Time frame: Up to approximately 27 months
Number of Participants With Grade Shift From Baseline in Hematology
Time frame: Up to approximately 27 months
Number of Participants With Grade Shift From Baseline in Plasma Chemistry
Time frame: Up to approximately 27 months
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Up to approximately 27 months
Change From Baseline in Pulse Rate
Time frame: Up to approximately 27 months
Change From Baseline in Temperature
Time frame: Up to approximately 27 months
Change From Baseline in Prothrombin International Normalized Ratio
Time frame: Baseline and up to approximately 27 months
Change in Baseline in Activated Partial Thromboplastin Time
Time frame: Baseline and up to approximately 27 months
Change From Baseline in Thyrotropin
Time frame: Baseline and up to approximately 27 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37890345Randall LM, O'Malley DM, Monk BJ, Coleman RL, Gaillard S, Adams S, Duska LR, Dalton H, Holloway RW, Huang M, Chon HS, Cloven NG, ElNaggar AC, O'Cearbhaill RE, Waggoner S, Tarkar A, Striha A, Nelsen LM, Baines A, Samnotra V, Konstantinopoulos PA. Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032). Gynecol Oncol. 2023 Nov;178:161-169. doi: 10.1016/j.ygyno.2023.10.005. Epub 2023 Oct 25.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
27 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib and Dostarlimab in people with Ovarian Neoplasms, run by Tesaro, Inc. at 27 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC) (time frame: Up to approximately 22 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03955471, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2022.