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Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Participants With Platinum Resistant Ovarian Cancer (MOONSTONE)

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ClinicalTrials.gov Identifier: NCT03955471
Recruitment Status : Suspended (This study has temporarily held recruitment activities to perform a pre-planned interim analysis. Other elements of this study are still ongoing.)
First Posted : May 20, 2019
Last Update Posted : October 9, 2020
Sponsor:
Collaborator:
Gynecologic Oncology Group
Information provided by (Responsible Party):
Tesaro, Inc.

Brief 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 gene (BRCA) mutation who have platinum-resistant disease and who have also been previously treated with bevacizumab.

Condition or disease Intervention/treatment Phase
Ovarian Neoplasms Drug: Niraparib Drug: TSR-042 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 3, 2019
Estimated Primary Completion Date : May 18, 2022
Estimated Study Completion Date : October 30, 2024


Arm Intervention/treatment
Experimental: Niraparib+TSR-042
Participants will receive both Niraparib and TSR-042 to evaluate the efficacy and safety of the combination of both drugs. Niraparib will be administered once daily (QD) continuously until Progressive disease (PD) or toxicity. Dostarlimab (TSR-042) will be administered via a 30-minute intravenous (IV) infusion on Day 1 every 3 weeks (Q3W) during Cycles 1 through 4. Beginning at Cycle 5, dostarlimab (TSR-042) will be administered via a 30-minute IV infusion on Day 1 of each 6-week cycle until PD or toxicity, for a maximum of 3 years.
Drug: Niraparib
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.
Other Name: ZEJULA

Drug: TSR-042
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).
Other Name: Dostarlimab




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]
    ORR is defined as the proportion of participants who have achieved confirmed complete response (CR) or partial response (PR), evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 based on Investigator assessment.


Secondary Outcome Measures :
  1. Duration of Response (DOR) [ Time Frame: Up to 5 years ]
    DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST v.1.1 based on Investigator assessment or death by any cause in the absence of progression by RECIST v.1.1.

  2. Progression-free Survival (PFS) [ Time Frame: Up to 5 years ]
    PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression by RECIST v.1.1 based on Investigator assessment or death by any cause in the absence of progression by RECIST v.1.1.

  3. Overall Survival (OS) [ Time Frame: Up to 5 years ]
    OS is defined as the time from the date of the first dose of study treatment to the date of death by any cause.

  4. Disease Control Rate (DCR) [ Time Frame: Up to 5 years ]
    DCR is defined as the percentage of patients 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.

  5. ORR Based on Independent Review Committee Assessment [ Time Frame: Up to 5 years ]
    ORR based on independent review committee assessment 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.

  6. DOR based on Independent Review Committee Assessment [ Time Frame: Up to 5 years ]
    DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST v.1.1 based on Independent Review Committee Assessment or death by any cause in the absence of progression by RECIST v.1.1.

  7. PFS based on Independent Review Committee Assessment [ Time Frame: Up to 5 years ]
    PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression by RECIST v.1.1 based on Independent Review Committee Assessment or death by any cause in the absence of progression by RECIST v.1.1.

  8. DCR based on Independent Review Committee Assessment [ Time Frame: Up to 5 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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.
  • 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. Slides cut from FFPE blocks are not acceptable.
  • Participant must agree to complete health-related quality of life (HRQoL) questionnaires throughout the study.

Exclusion Criteria:

  • Participant who experienced disease progression within 3 months of first-line platinum therapy.
  • Participants with a known 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.
  • Participant has not recovered from prior chemotherapy induced adverse events (AEs).
  • 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 study 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:

    1. Cluster of differentiation 4 >=350/μL and viral load <400 copies/milliliter (mL)
    2. No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment
    3. No history of HIV-associated malignancy for the past 5 years
    4. 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.

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): NCT03955471


Locations
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United States, Arizona
GSK Investigational Site
Scottsdale, Arizona, United States, 85258
GSK Investigational Site
Tucson, Arizona, United States, 85711
United States, California
GSK Investigational Site
Duarte, California, United States, 91010
GSK Investigational Site
Long Beach, California, United States, 90806
GSK Investigational Site
Newport Beach, California, United States, 92663
GSK Investigational Site
Orange, California, United States, 92868
GSK Investigational Site
San Francisco, California, United States, 94158
GSK Investigational Site
Solvang, California, United States, 93463
United States, Florida
GSK Investigational Site
Coral Gables, Florida, United States, 33146
GSK Investigational Site
Deerfield Beach, Florida, United States, 33442
GSK Investigational Site
Miami, Florida, United States, 33136
GSK Investigational Site
Orlando, Florida, United States, 32804
GSK Investigational Site
Tampa, Florida, United States, 33612
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60612
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46250
United States, Iowa
GSK Investigational Site
Iowa City, Iowa, United States, 52242-1009
United States, Louisiana
GSK Investigational Site
Covington, Louisiana, United States, 70433
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21287
GSK Investigational Site
Silver Spring, Maryland, United States, 20902
GSK Investigational Site
Silver Spring, Maryland, United States, 20910
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02114
GSK Investigational Site
Boston, Massachusetts, United States, 02215
GSK Investigational Site
Burlington, Massachusetts, United States, 01805
United States, Minnesota
GSK Investigational Site
Maplewood, Minnesota, United States, 55109
GSK Investigational Site
Minneapolis, Minnesota, United States, 55404
United States, Mississippi
GSK Investigational Site
Jackson, Mississippi, United States, 39216
United States, New Mexico
GSK Investigational Site
Albuquerque, New Mexico, United States, 87131
United States, New York
GSK Investigational Site
Harrison, New York, United States, 10604
GSK Investigational Site
New York, New York, United States, 10022
GSK Investigational Site
New York, New York, United States, 10065
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27710
United States, Ohio
GSK Investigational Site
Cleveland, Ohio, United States, 44106
GSK Investigational Site
Cleveland, Ohio, United States, 44195
GSK Investigational Site
Columbus, Ohio, United States, 43210
United States, Oregon
GSK Investigational Site
Eugene, Oregon, United States, 97401
United States, Pennsylvania
GSK Investigational Site
Willow Grove, Pennsylvania, United States, 19090
United States, Rhode Island
GSK Investigational Site
Providence, Rhode Island, United States, 02905
United States, Tennessee
GSK Investigational Site
Chattanooga, Tennessee, United States, 37403
GSK Investigational Site
Germantown, Tennessee, United States, 38138
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78731
GSK Investigational Site
Fort Worth, Texas, United States, 76104
GSK Investigational Site
San Antonio, Texas, United States, 78229
GSK Investigational Site
The Woodlands, Texas, United States, 77380
United States, Virginia
GSK Investigational Site
Charlottesville, Virginia, United States, 22903
Sponsors and Collaborators
Tesaro, Inc.
Gynecologic Oncology Group
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT03955471    
Other Study ID Numbers: 213353
3000-02-006 ( Other Identifier: Tesaro )
First Posted: May 20, 2019    Key Record Dates
Last Update Posted: October 9, 2020
Last Verified: October 2020
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.:
Open-label
Single-arm
Efficacy and Safety
Platinum-resistant ovarian cancer
Niraparib
dostarlimab
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 Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents