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

• Status: Completed
• Trial end date: 2022-04-01
• Target enrollment: 0
• Participant gender: Female

Summary

The primary objective of this sub study is to evaluate the efficacy of the combination of TSR-042, bevacizumab, and niraparib in participants with advanced, relapsed, high-grade ovarian, fallopian tube, or primary peritoneal cancer who have received 1 to 2 prior lines of anticancer therapy, are PARP inhibitor naïve, and have platinum-resistant but not refractory disease.

This study is a sub study of the master protocol - OPAL (NCT03574779).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tesaro, Inc.
• Treatments: Bevacizumab; Niraparib

Criteria

Inclusion Criteria:

• Participant must be resistant to the most recent platinum-based therapy, defined for the purpose of this protocol as progression within 6 months from completion of a minimum of 4 cycles of platinum-containing therapy. This should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing disease progression. Participant with primary platinum-refractory disease as defined by those who progressed during or within 4 weeks of completion of first platinum-based chemotherapy are not eligible

• Participant must not have received any prior therapy for ovarian cancer with a PARP inhibitor

• Participant has had 1 to 2 prior lines of anticancer therapy for ovarian cancer

• Participant is able to take oral medications.

Exclusion Criteria:

• Participant has known hypersensitivity to TSR-042, bevacizumab, niraparib, their components, or their excipients

• Participant has a known history of myelodysplastic syndrome or acute myeloid leukemia

• 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.

• Participant received prior treatment with an anti- programmed death-1 (PD-1) or anti- programmed death-ligand 1 (PD-L1) agent

• Participant has received prior treatment with anti-angiogenic therapy with the exception of bevacizumab. (Participant who received prior bevacizumab are eligible only if they did not discontinue bevacizumab due to toxicity, as established by the Investigator.)

• Participant has bowel obstruction, had bowel obstruction within the past 3 months, or is otherwise judged by the Investigator to be at high risk for bowel obstruction related to the underlying disease. Participant has any history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or significant bowel involvement on computed tomography scan

• Participant has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (Participant discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate <2g of protein in 24 hours to be eligible.)

• Participant is at increased bleeding risk due to concurrent conditions (eg, major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months)

• Participant has a history of recent major thromboembolic event defined as follows:

1. Pulmonary embolism diagnosed within 3 months of enrollment

2. Lower extremity deep venous thrombosis diagnosed within 3 months of enrollment (Participant with a history of thromboembolic disease on stable therapeutic anticoagulation for more than 3 months prior to enrollment are eligible for this study.)