Ovarian NeoplasmPhase 2COHORT-ANCT05751629
Study to Evaluate the Safety and Efficacy of TSR-042, Bevacizumab, and Niraparib in Participants With Recurrent Ovarian Cancer
A Phase 2 study testing Dostarlimab, Bevacizumab and Niraparib in people with Ovarian Neoplasm, run by Tesaro, Inc. at 10 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Neoplasm
- What is being tested?
- Dostarlimab, Bevacizumab and Niraparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 10 sitesUnited States
- Study dates
- 15 Nov 2018to 1 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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.)
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
GSK Investigational Site
Birmingham, Alabama, 35249
GSK Investigational Site
Boston, Massachusetts, 02114
GSK Investigational Site
Boston, Massachusetts, 02215
GSK Investigational Site
Chicago, Illinois, 60637
GSK Investigational Site
Durham, North Carolina, 27710
GSK Investigational Site
Los Angeles, California, 90095
GSK Investigational Site
Oklahoma City, Oklahoma, 73104
GSK Investigational Site
Palo Alto, California, 94304
GSK Investigational Site
Rochester, Minnesota, 55905
GSK Investigational Site
Ventura, California, 93003
About this study
Official title: Cohort A: PARP Inhibitor-Naïve Platinum-Resistant Ovarian Cancer Treatment Cohort With TSR-042, Bevacizumab, and Niraparib
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
- Being tested
- Dostarlimab, Bevacizumab, Niraparib
- Keywords
- Poly-ADP-ribose polymerase (PARP) Inhibitor, Ovarian cancer, Niraparib, Bevacizumab, TSR-042, Neoadjuvant treatment
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DostarlimabDrug
Also called TSR-042
Dostarlimab was administered.
BevacizumabDrug
Also called Avastin
Bevacizumab was administered.
NiraparibDrug
Also called ZEJULA
Niraparib was administered.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (Dostarlimab + Bevacizumab + Niraparib) | Experimental | Not described Receives: Drug: Dostarlimab; Drug: Bevacizumab; Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to approximately 38 Months
Secondary outcomes (10)
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.
Measured: Up to approximately 38 Months
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.
Measured: Up to approximately 38 Months
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).
Measured: Up to approximately 38 Months
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.
Measured: Up to approximately 38 Months
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.
Measured: Up to approximately 38 Months
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.
Measured: Up to approximately 38 Months
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.
Measured: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
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.
Measured: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
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.
Measured: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
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.
Measured: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2023
- Study start15 Nov 2018
- Primary completion1 Apr 2022
- Study completion1 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ovarian NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tesaro, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05751629
- Sponsor's protocol ID
- 213357-COHORT-A
- Acronym
- COHORT-A
- Status last verified
- Feb 2023
- First submitted
- 20 Feb 2023
- Last updated
- 21 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cohort A: PARP Inhibitor-Naïve Platinum-Resistant Ovarian Cancer Treatment Cohort With TSR-042, Bevacizumab, and Niraparib
- ClinicalTrials.gov ID
- NCT05751629
- Acronym / sponsor ID
- COHORT-A / 213357-COHORT-A
- Conditions
- Ovarian Neoplasm
- Keywords
- Poly-ADP-ribose polymerase (PARP) Inhibitor, Ovarian cancer, Niraparib, Bevacizumab, TSR-042, Neoadjuvant treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Tesaro, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Nov 2018 (actual)
- Primary completion
- 1 Apr 2022 (actual)
- Study completion
- 1 Apr 2022 (actual)
- First posted
- 2 Mar 2023 (actual)
- Results
- Posted 21 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort A (Dostarlimab + Bevacizumab + Niraparib) | Experimental | Drug: Dostarlimab, Drug: Bevacizumab, Drug: Niraparib |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DostarlimabAlso: TSR-042Dostarlimab was administered. | Drug | Cohort A (Dostarlimab + Bevacizumab + Niraparib) |
| BevacizumabAlso: AvastinBevacizumab was administered. | Drug | Cohort A (Dostarlimab + Bevacizumab + Niraparib) |
| NiraparibAlso: ZEJULANiraparib was administered. | Drug | Cohort A (Dostarlimab + Bevacizumab + Niraparib) |
Primary outcome
Confirmed Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Time frame: Up to approximately 38 Months
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).
10 secondary outcomes
Progression Free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment
Time frame: Up to approximately 38 Months
Overall Survival (OS)
Time frame: Up to approximately 38 Months
Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment
Time frame: Up to approximately 38 Months
Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment
Time frame: Up to approximately 38 Months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to approximately 38 Months
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters - Chemistry, Coagulation, Hematology and Thyroid
Time frame: Up to approximately 38 Months
Absolute Values in Urinalysis Parameter - Specific Gravity (Ratio)
Time frame: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
Change From Baseline in Cancer Antigen 125 (CA-125) at End of Treatment
Time frame: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
Change From Baseline in Vital Signs (Weight) at End of Treatment
Time frame: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline and End of Treatment
Time frame: Baseline (Day 1) and end of treatment (Up to approximately 32 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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/
Related trials for Ovarian Neoplasm
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Recruiting
A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer
Ovarian Carcinoma
RecruitingPhase 2
Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer
Ovarian Cancer, Fallopian Tube Cancer
Active, not recruitingPhase 1/2
Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Can...
Colorectal Neoplasms, Breast Neoplasms
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dostarlimab, Bevacizumab and Niraparib in people with Ovarian Neoplasm, run by Tesaro, Inc. at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Confirmed Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment (time frame: Up to approximately 38 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2023.