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

Sponsor

Tesaro, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT05751629

Collaborator

(none)

Enrollment

Locations

Arm

40.5

Actual Duration (Months)

4.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Ovarian Neoplasm	Drug: Dostarlimab Drug: Bevacizumab Drug: Niraparib	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cohort A: PARP Inhibitor-Naïve Platinum-Resistant Ovarian Cancer Treatment Cohort With TSR-042, Bevacizumab, and Niraparib

Actual Study Start Date :

Nov 15, 2018

Actual Primary Completion Date :

Apr 1, 2022

Actual Study Completion Date :

Apr 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A (Dostarlimab + Bevacizumab + Niraparib)	Drug: Dostarlimab Dostarlimab was administered. Other Names: TSR-042 Drug: Bevacizumab Bevacizumab was administered. Other Names: Avastin Drug: Niraparib Niraparib was administered. Other Names: ZEJULA

Arm

Intervention/Treatment

Experimental: Cohort A (Dostarlimab + Bevacizumab + Niraparib)

Drug: Dostarlimab

Dostarlimab was administered.

Other Names:

TSR-042

Drug: Bevacizumab

Bevacizumab was administered.

Other Names:

Avastin

Drug: Niraparib

Niraparib was administered.

Other Names:

ZEJULA

Outcome Measures

Primary Outcome Measures

Confirmed Objective response rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment [Up to 38 Months]
ORR is defined as percentage of participants who have achieved 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 1.1. 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).

Secondary Outcome Measures

Progression free survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment [Up to 38 Months]
PFS is defined as the time from the date of the first dose of study treatment to the earliest date of assessment of progression or death by any cause in the absence of progression by RECIST version 1.1. Disease Progression is defined 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) [Up to 38 Months]
OS is defined as the time from the date of the first dose of study treatment to the date of death due to any cause.
Duration of response (DOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment [Up to 38 Months]
DOR is 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 [Up to 38 Months]
DCR is 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) [Up to 38 Months]
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 Participant with Clinically Significant Changes in Clinical Laboratory Parameters - Chemistry, Coagulation, Hematology and Thyroid [Up to 38 Months]
Change from Baseline in Urinalysis Parameter - Specific Gravity (Ratio) [Up to 38 Months]
Change from Baseline in Cancer Antigen 125 (Units per milliliter [U/mL]) [Up to 38 Months]
Change from Baseline in Vital Signs - Weight (Kilogram) [Up to 38 Months]
Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status [Up to 38 Months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35249
2	GSK Investigational Site	Los Angeles	California	United States	90095
3	GSK Investigational Site	Palo Alto	California	United States	94304
4	GSK Investigational Site	Ventura	California	United States	93003
5	GSK Investigational Site	Chicago	Illinois	United States	60637
6	GSK Investigational Site	Boston	Massachusetts	United States	02114
7	US GSK Clinical Trials	Boston	Massachusetts	United States	02215
8	GSK Investigational Site	Rochester	Minnesota	United States	55905
9	GSK Investigational Site	Durham	North Carolina	United States	27710
10	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73104