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Clinical Trial 20137

Cancer Type: Gynecological Tumor
Interventions:Niraparib; TSR-042

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Hye Sook Chon

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase 2 Open-Label, Single-Arm Study To Evaluate the Efficacy and Safety of the Combination OF Niraparib and TSR-042 in Patients with Platinum-Resistant Ovarian Cancer (MOONSTONE)

Summary

This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and TSR-042 in patients with advanced, relapsed, high-grade ovarian, fallopian tube, or primary peritoneal cancer without known BRCA mutation who have platinum-resistant disease and who have also been previously treated with bevacizumab.

Objective

Primary Objective: The primary objective of this study is to evaluate the efficacy, as measured by confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on Investigator assessment, of the combination of niraparib and TSR-042 in patients with platinum-resistant ovarian cancer (PROC) without a known germline breast cancer susceptibility gene (gBRCA) mutation who have been previously treated with bevacizumab. Secondary Objectives: To evaluate the overall clinical benefit of the niraparib and TSR-042 combination as measured by the following secondary endpoints: − duration of response (DOR) per RECIST v1.1 based on Investigator assessment − progression-free survival (PFS) per RECIST v1.1 based on Investigator assessment − overall survival (OS) − disease control rate (DCR), defined as the percentage of patients who have achieved best overall response (BOR) of confirmed partial response (PR), complete response (CR), or stable disease (SD) per RECIST v1.1 based on Investigator assessment. To evaluate the ORR per RECIST v1.1 based on independent review committee assessment, To evaluate the safety and tolerability of the niraparib and TSR-042 combination in patients with PROC as measured by standard safety assessments Exploratory Objectives: To evaluate efficacy of the niraparib and TSR-042 combination among patients with documented BRCAwt tumors (excluding patients with tBRCA mutations and unknown tBRCA status), as measured by confirmed ORR, DOR, PFS, OS, and DCR based on Investigator assessment using RECIST v1.1. To evaluate the duration of disease control among patients with BOR of CR, PR, or SD based on Investigator assessment and independent review committee assessment, To evaluate health-related quality of life (HRQoL) in patients with PROC treated with the combination of niraparib and TSR-042, as measured by the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). To identify additional potential disease-related or treatment-related biomarkers that correlate with responses to the niraparib and TSR-042 combination, including, but not limited to, the measures of homologous recombination repair (HRR) pathway defects

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 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 is willing to undergo a pre-treatment tumor biopsy if an appropriate archival tumor tissue sample is not available.
  • Participant must agree to complete HRQoL questionnaires throughout the study.

  • Exclusion Criteria

  • Participant who experienced disease progression within 3 months of first-line platinum therapy.
  • Known BRCA 1 or 2 mutation.
  • Has received prior therapy with an anti-PD-1 or anti-PD-2 agent.
  • Has a known hypersensitivity to TSR-042, Niraparib, their components, or their excipients.
  • Has a known history of myelodysplastic syndrome or acute myeloid leukemia.
  • Has not recovered from prior chemotherapy induced AE's.
  • 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.
  • Is participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment.
  • 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.
  • Has received live vaccine within 30 days of planned start of study therapy
  • Has symptomatic uncontrolled brain or leptomeningeal metastases. (If investigator feels participant symptoms are not symptomatic participants can undergo a scan to confirm for eligibility).
  • Major surgery with 4 weeks of starting the study.
  • 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.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
  • Known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus ribonucleic acid, qualitative).
  • Known history of human immunodeficiency virus.