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

Primary Purpose

Ovarian Neoplasm

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dostarlimab
Bevacizumab
Niraparib
Sponsored by
Tesaro, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Neoplasm focused on measuring Poly-ADP-ribose polymerase (PARP) Inhibitor, Ovarian cancer, Niraparib, Bevacizumab, TSR-042, Neoadjuvant treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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: 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.)

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cohort A (Dostarlimab + Bevacizumab + Niraparib)

Arm Description

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Progression Free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment
PFS was defined as the time from the date of the first dose of study treatment to the earliest date of assessment of disease progression or death by any cause in the absence of progression by RECIST v1.1. Disease Progression is defined using RECIST v1.1 as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Overall Survival (OS)
OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. Median and 95% CI are presented.
Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment
DOR was defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 based on Investigator's assessment or death by any cause. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm).
Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment
DCR was defined as the percentage of participants who have achieved best overall response of CR, PR, or stable disease (SD) per RECIST version 1.1 based on Investigator's assessment. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters - Chemistry, Coagulation, Hematology and Thyroid
Blood samples were collected for the analysis of clinical laboratory parameters - chemistry, coagulation, hematology and thyroid.
Absolute Values in Urinalysis Parameter - Specific Gravity (Ratio)
Urine samples were collected at indicated time points for the assessment of specific gravity. Baseline is defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Change From Baseline in Cancer Antigen 125 (CA-125) at End of Treatment
Blood samples were collected for the analysis of CA-125. Baseline is defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Change From Baseline in Vital Signs (Weight) at End of Treatment
Weight was measured in ordinary indoor clothing (without shoes) and was recorded at specified study visit. Baseline is defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment
Performance status assessments were based on 5-grade ECOG scale (from 0 to 4), where 0=fully active, able to carry on all pre-disease performance without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work); 2=ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed or chair. Baseline is defined as the most recent non-missing measurement prior to or on the first administration of study drug.

Full Information

First Posted
February 20, 2023
Last Updated
March 29, 2023
Sponsor
Tesaro, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05751629
Brief Title
Study to Evaluate the Safety and Efficacy of TSR-042, Bevacizumab, and Niraparib in Participants With Recurrent Ovarian Cancer
Acronym
COHORT-A
Official Title
Cohort A: PARP Inhibitor-Naïve Platinum-Resistant Ovarian Cancer Treatment Cohort With TSR-042, Bevacizumab, and Niraparib
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
November 15, 2018 (Actual)
Primary Completion Date
April 1, 2022 (Actual)
Study Completion Date
April 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tesaro, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Neoplasm
Keywords
Poly-ADP-ribose polymerase (PARP) Inhibitor, Ovarian cancer, Niraparib, Bevacizumab, TSR-042, Neoadjuvant treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A (Dostarlimab + Bevacizumab + Niraparib)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Dostarlimab
Other Intervention Name(s)
TSR-042
Intervention Description
Dostarlimab was administered.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab was administered.
Intervention Type
Drug
Intervention Name(s)
Niraparib
Other Intervention Name(s)
ZEJULA
Intervention Description
Niraparib was administered.
Primary Outcome Measure Information:
Title
Confirmed Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Description
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).
Time Frame
Up to approximately 38 Months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment
Description
PFS was defined as the time from the date of the first dose of study treatment to the earliest date of assessment of disease progression or death by any cause in the absence of progression by RECIST v1.1. Disease Progression is defined using RECIST v1.1 as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame
Up to approximately 38 Months
Title
Overall Survival (OS)
Description
OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. Median and 95% CI are presented.
Time Frame
Up to approximately 38 Months
Title
Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment
Description
DOR was defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 based on Investigator's assessment or death by any cause. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm).
Time Frame
Up to approximately 38 Months
Title
Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment
Description
DCR was defined as the percentage of participants who have achieved best overall response of CR, PR, or stable disease (SD) per RECIST version 1.1 based on Investigator's assessment. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame
Up to approximately 38 Months
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
Time Frame
Up to approximately 38 Months
Title
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters - Chemistry, Coagulation, Hematology and Thyroid
Description
Blood samples were collected for the analysis of clinical laboratory parameters - chemistry, coagulation, hematology and thyroid.
Time Frame
Up to approximately 38 Months
Title
Absolute Values in Urinalysis Parameter - Specific Gravity (Ratio)
Description
Urine samples were collected at indicated time points for the assessment of specific gravity. Baseline is defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Time Frame
Baseline (Day 1) and end of treatment (Up to approximately 32 months)
Title
Change From Baseline in Cancer Antigen 125 (CA-125) at End of Treatment
Description
Blood samples were collected for the analysis of CA-125. Baseline is defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Time Frame
Baseline (Day 1) and end of treatment (Up to approximately 32 months)
Title
Change From Baseline in Vital Signs (Weight) at End of Treatment
Description
Weight was measured in ordinary indoor clothing (without shoes) and was recorded at specified study visit. Baseline is defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Time Frame
Baseline (Day 1) and end of treatment (Up to approximately 32 months)
Title
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment
Description
Performance status assessments were based on 5-grade ECOG scale (from 0 to 4), where 0=fully active, able to carry on all pre-disease performance without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work); 2=ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed or chair. Baseline is defined as the most recent non-missing measurement prior to or on the first administration of study drug.
Time Frame
Baseline (Day 1) and end of treatment (Up to approximately 32 months)

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Female participants will be included.
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
GSK Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
GSK Investigational Site
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
GSK Investigational Site
City
Ventura
State/Province
California
ZIP/Postal Code
93003
Country
United States
Facility Name
GSK Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
GSK Investigational Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
GSK Investigational Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
GSK Investigational Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
http://www.gsk.com/en-gb/innovation/trials/data-transparency/

Learn more about this trial

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

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