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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-03

Study Completion Date

2022-01-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

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

NCT03602859

Ovarian Neoplasms Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma

ACTIVE_NOT_RECRUITING PHASE3

Study to Evaluate the Safety and Efficacy of TSR-042, Bevacizumab, and Niraparib in Participants With Recurrent Ovarian Cancer

NCT05751629

Ovarian Neoplasm

COMPLETED PHASE2

Study to Estimate Efficacy of Combining Dostarlimab and Niraparib in Relapsed EOC After Treatment With PARPi

NCT05126342

Recurrent Ovarian Cancer Recurrent Fallopian Tube Cancer Primary Peritoneal Cancer

WITHDRAWN PHASE2

Recurrent Ovarian CarcinoSarcoma Anti-pd-1 Niraparib

NCT03651206

Ovarian Carcinosarcoma Endometrial Carcinosarcoma

RECRUITING PHASE2/PHASE3

A Study of Niraparib in Patients With Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens

NCT02354586

Ovarian Neoplasms Ovarian Cancer

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Ovarian Neoplasms

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Niraparib+Dostarlimab (TSR-042)

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.

Group Type EXPERIMENTAL

Niraparib

Intervention Type DRUG

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.

Dostarlimab

Intervention Type DRUG

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).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Dostarlimab

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).

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

ZEJULA

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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. 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.

Exclusion Criteria

* 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.
* 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:

1. Cluster of differentiation 4 \>=350/microliter (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.

Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No