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

NCT05751629 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 213357-COHORT-A
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 10

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).

Conditions

Ovarian Neoplasm

Keywords

Poly-ADP-ribose polymerase (PARP) Inhibitor; Ovarian cancer; Niraparib; Bevacizumab; TSR-042; Neoadjuvant treatment

Outcome Measures

Primary Outcomes (1)

• Confirmed Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

  ORR was defined as percentage of participants with a confirmed investigator-assessed Best Overall Response (BOR) of confirmed complete response (CR) or partial response (PR), evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm).

  Up to approximately 38 Months

Secondary Outcomes (10)

• Progression Free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment

  Up to approximately 38 Months

• Overall Survival (OS)

  Up to approximately 38 Months

• Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment

  Up to approximately 38 Months

• Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment

  Up to approximately 38 Months

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Up to approximately 38 Months

Study Arms (1)

Cohort A (Dostarlimab + Bevacizumab + Niraparib)

EXPERIMENTAL

Drug: Dostarlimab; Drug: Bevacizumab; Drug: Niraparib

Interventions

Dostarlimab DRUG

Dostarlimab was administered.

Also known as: TSR-042

Cohort A (Dostarlimab + Bevacizumab + Niraparib)

Bevacizumab DRUG

Bevacizumab was administered.

Also known as: Avastin

Cohort A (Dostarlimab + Bevacizumab + Niraparib)

Niraparib DRUG

Niraparib was administered.

Also known as: ZEJULA

Cohort A (Dostarlimab + Bevacizumab + Niraparib)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female participants will be included.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Pulmonary embolism diagnosed within 3 months of enrollment
• 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.)

Sponsors & Collaborators

• Tesaro, Inc.: lead

Study Sites (10)

GSK Investigational Site

Birmingham, Alabama, 35249, United States

Location

GSK Investigational Site

Los Angeles, California, 90095, United States

Location

GSK Investigational Site

Palo Alto, California, 94304, United States

Location

GSK Investigational Site

Ventura, California, 93003, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

dostarlimab; Bevacizumab; niraparib

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: February 20, 2023
• First Posted: March 2, 2023
• Study Start: November 15, 2018
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: April 21, 2023
• Results First Posted: April 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

US (10)