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

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.

Inclusion Criteria

• Patient 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.
• Patients must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer.
• Patients must be considered resistant to the last administered platinum therapy.
• Patients must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer.
• Patients must have been previously treated with platinum-based regimen, taxane agent(s), and bevacizumab.
• Patient has measurable disease according to RECIST v.1.1.
• Patient has an ECOG performance status of 0 or 1.
• Patient has adequate organ function.
• Females with childbearing potential have a serum pregnancy test that is negative 72 prior first dose and are not breastfeeding. Patient must also agree to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment.
• Patient is willing to undergo a pre-treatment tumor biopsy if an appropriate archival tumor tissue sample is not available.
• Patient must agree to complete HRQoL questionnaires throughout the study.

Exclusion Criteria

• Patient who experienced disease progression within 3 months of first-line platinum therapy.
• Patients with a known BRCA 1 or 2 mutation.
• Patient has received prior therapy with an anti-PD-1 or anti-PD-2 agent.
• Patient has a known hypersensitivity to TSR-042, Niraparib, their components, or their excipients.
• Patient has a known history of myelodysplastic syndrome or acute myeloid leukemia.
• Patient has not recovered from prior chemotherapy induced AE's.
• Patient 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.
• Patient 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.
• Patient 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.
• Patient has received live vaccine within 30 days of planned start of study therapy
• Patient has symptomatic uncontrolled brain or leptomeningeal metastases. (If investigator feels patient symptoms are not symptomatic patients can undergo a scan to confirm for eligibility).
• Patient had major surgery with 4 weeks of starting the study.
• Patient has a known additional malignancy that progressed or required active treatment within the last 2 years.
• Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active controlled infection.
• Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
• Patient has known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus ribonucleic acid, qualitative).
• Patient has a known history of human immunodeficiency virus.

Lead Organization
Tesaro Inc

Primary ID 3000-02-006
Secondary IDs NCI-2019-04861
Clinicaltrials.gov ID NCT03955471