Clinical trial NCT05751629: Study to Evaluate the Safety and Efficacy of TSR-042, Bevacizumab, and Niraparib in Participants With Recurrent Ovarian Cancer
Official title: Cohort A: PARP Inhibitor-Naïve Platinum-Resistant Ovarian Cancer Treatment Cohort With TSR-042, Bevacizumab, and Niraparib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Neoplasm
Keywords: Poly-ADP-ribose polymerase (PARP) Inhibitor
Ovarian cancer
Niraparib
Bevacizumab
TSR-042
Neoadjuvant treatment
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-02
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


Eligibility 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.)

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
timeFrame: Up to approximately 38 Months
Secondary outcomes:
measure: Progression Free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment
timeFrame: Up to approximately 38 Months
measure: Overall Survival (OS)
timeFrame: Up to approximately 38 Months
measure: Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment
timeFrame: Up to approximately 38 Months
measure: Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment
timeFrame: Up to approximately 38 Months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 38 Months
measure: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters - Chemistry, Coagulation, Hematology and Thyroid
timeFrame: Up to approximately 38 Months
measure: Absolute Values in Urinalysis Parameter - Specific Gravity (Ratio)
timeFrame: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
measure: Change From Baseline in Cancer Antigen 125 (CA-125) at End of Treatment
timeFrame: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
measure: Change From Baseline in Vital Signs (Weight) at End of Treatment
timeFrame: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
measure: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment
timeFrame: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Palo Alto
country: United States
facility: GSK Investigational Site
state: California
city: Ventura
country: United States
facility: GSK Investigational Site
state: California
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: