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

NCT03955471 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2133533000-02-006
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 27

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.

Conditions

Ovarian Neoplasms

Keywords

Open-label; Single-arm; Efficacy and Safety; Platinum-resistant ovarian cancer; Niraparib; dostarlimab

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to approximately 22 months

Secondary Outcomes (25)

• Duration of Response (DOR) in Participants With PROC

  Up to approximately 22 months

• DOR in Participants With PROC Who Have PD-L 1 Positive Status

  Up to approximately 22 months

• Progression-free Survival (PFS) in Participants With PROC

  Up to approximately 22 months

• PFS in Participants With PROC Who Have PD-L 1 Positive Status

  Up to approximately 22 months

• Overall Survival (OS) in Participants With PROC

  Up to approximately 22 months

Study Arms (1)

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.

Drug: Niraparib; Drug: Dostarlimab

Interventions

Niraparib 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.

Also known as: ZEJULA

Niraparib+Dostarlimab (TSR-042)

Dostarlimab 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).

Niraparib+Dostarlimab (TSR-042)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tesaro, Inc.: lead
• Gynecologic Oncology Group: collaborator

Study Sites (27)

GSK Investigational Site

Scottsdale, Arizona, 85258, United States

Location

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

Newport Beach, California, 92663, United States

Location

GSK Investigational Site

Orange, California, 92868, United States

Location

GSK Investigational Site

Solvang, California, 93463, United States

Location

GSK Investigational Site

Deerfield Beach, Florida, 33442, United States

Location

GSK Investigational Site

Miami, Florida, 33136, United States

Location

GSK Investigational Site

Orlando, Florida, 32804, United States

Location

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Iowa City, Iowa, 52242-1009, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

Burlington, Massachusetts, 01805, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55404, United States

Location

GSK Investigational Site

Jackson, Mississippi, 39216, United States

Location

GSK Investigational Site

New York, New York, 10022, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44124, United States

Location

GSK Investigational Site

Eugene, Oregon, 97401, United States

Location

GSK Investigational Site

Providence, Rhode Island, 02905, United States

Location

GSK Investigational Site

Chattanooga, Tennessee, 37403, United States

Location

GSK Investigational Site

Germantown, Tennessee, 38138, United States

Location

GSK Investigational Site

Austin, Texas, 78731, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Charlottesville, Virginia, 22903, United States

Location

Related Publications (1)

• 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.

  PMID: 37890345 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

niraparib; dostarlimab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2019
• First Posted: May 20, 2019
• Study Start: October 3, 2019
• Primary Completion: August 18, 2021
• Study Completion: January 12, 2022
• Last Updated: September 10, 2022
• Results First Posted: September 10, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (27)