A Study to Evaluate the Efficacy and Safety of Novel Treatment Combinations in Participants With Ovarian Cancer
OPAL
A Phase 1B/2 Multicohort Umbrella Study to Evaluate the Safety and Efficacy of Novel Treatments And/Or Combinations of Treatments in Participants With Ovarian Cancer (OPAL)
2 other identifiers
interventional
77
3 countries
28
Brief Summary
This study will evaluate the efficacy and safety of niraparib and novel treatment combinations of niraparib as described within each cohort-specific supplement in participants with ovarian, fallopian tube, or primary peritoneal cancer. Cohort A (single arm) includes participants with recurrent ovarian cancer. Cohort B will not be initiated. Cohort C (randomized-2 arms) includes participants with newly diagnosed ovarian cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Nov 2018
Longer than P75 for phase_2
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 14, 2018
CompletedFirst Posted
Study publicly available on registry
July 2, 2018
CompletedStudy Start
First participant enrolled
November 15, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 28, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2025
CompletedResults Posted
Study results publicly available
July 15, 2025
CompletedJuly 15, 2025
June 1, 2025
5.6 years
May 14, 2018
June 25, 2025
June 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Enrolled Across Cohorts
Number of Participants enrolled across cohorts are presented.
Day 1
Study Arms (3)
Cohort A: 1-2 prior lines of therapy (TSR-042, Bevacizumab, and Niraparib)
EXPERIMENTALPARP Inhibitor-Naive Platinum-Resistant Ovarian Cancer Treatment Cohort with TSR-042, Bevacizumab, and Niraparib. TSR-042 administered 500 milligrams (mg) on Day 1 every 3 weeks (Q3W) for 4 cycles (each cycle is 21 days), followed by 1000 mg every 6 weeks (Q6W) beginning on Cycle 5 Day 1 until progressive disease (PD) or toxicity. Bevacizumab administered 15 milligram per kilogram (mg/kg) every 3 weeks for up to 15 months. Niraparib 200 or 300 mg per day until PD or toxicity.
Cohort C: Arm 1: Participants receiving platinum plus taxane
ACTIVE COMPARATORParticipants are expected to receive 1 run-in cycle (up to 5 weeks) of carboplatin-paclitaxel during pre-screening. After confirmation that the tumor is homologous recombination-deficient (HRd). Participants will then be randomized to three 21-day cycles of platinum-taxane doublet chemotherapy (carboplatin plus paclitaxane). After interval debulking surgery (IDS), all participants will receive up to three 21-day cycles of adjuvant platinum-taxane doublet chemotherapy (and optional bevacizumab for participants deemed high-risk; third cycle is optional) followed by niraparib (and optional bevacizumab or bevacizumab biosimilar for participants deemed high- risk) maintenance treatment.
Cohort C: Arm 2: Participants receiving neoadjuvant Niraparib
EXPERIMENTALParticipants are expected to receive 1 run-in cycle (up to 5 weeks) of carboplatin-paclitaxel during pre-screening. After confirmation that the tumor is HRd, participants will be randomized to three 21-day cycles of neoadjuvant niraparib therapy. After IDS, all participants will receive up to three 21-day cycles of adjuvant platinum-taxane doublet chemotherapy (and optional bevacizumab for participants deemed high-risk; third cycle is optional) followed by niraparib (and optional bevacizumab or bevacizumab biosimilar for participants deemed high- risk) maintenance treatment.
Interventions
Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for participants with tumors that harbor defects in the homologous recombination deoxyribonucleic acid (DNA) repair pathway or that are driven by PARP-mediated transcription factors.
TSR-042 is a humanized monoclonal antibody that binds with high affinity to Programmed cell death protein 1 (PD-1) resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).
Bevacizumab is an Food Drug and Administration (FDA) approved antiangiogenic recombinant humanized monoclonal Immunoglobulin (Ig) G1 antibody against the vascular endothelial growth factor protein, which has been shown to be efficacious against a variety of different cancer types, including colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma.
Carboplatin will be infused intravenously over 60 minutes at the prescribed dose of area under the concentration versus time curve of 5 to 6 mg/milliliters (mL) per minute on Day 1 of every 21-day cycle
Paclitaxel will be administered intravenously over 180 minutes at the prescribed dose of 175 mg/meter square (m\^2) on Day 1 of every 21-day cycle
Eligibility Criteria
You may qualify if:
- Participants must have the following histologic diagnosis unless otherwise specified in a cohort-specific supplement:
- Phase 2 cohorts: Participant has histologically diagnosed high-grade recurrent epithelial (that is \[i.e.\], serous, endometrioid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer or carcinosarcoma of the ovary. Participant with high-grade mixed histology is also eligible.
- For the Phase 1B components: Participant has histologically diagnosed gynecologic malignancy (i.e., any cancer that started in a woman's reproductive system). Gynecologic malignancies include cervical cancer; endometrial cancer; vaginal cancer; vulvar cancer; high-grade recurrent epithelial (i.e., serous, endometrioid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer; or advanced carcinosarcoma of the ovary. Participant with high-grade mixed histology is also eligible.
- The allowed number of prior lines of anticancer therapy for primary cancer will be specified in each cohort-specific supplement. Treatment with hormonal agents alone are not counted in the number of lines of therapy. Treatment with single-agent bevacizumab or PARP inhibitors given as maintenance is not counted as a separate line of therapy. If a therapeutic regimen is modified or changed for a reason other than lack of response or PD (such as allergic reaction, toxicity, or drug availability), this is not counted as a separate line of therapy.
- Phase 2 cohorts: Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Participant has adequate organ function, defined as follows:
- Absolute neutrophil count \>=1500 per microliter (/mcL), without growth factor support (granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor administration is not permitted within 2 weeks prior to screening).
- Platelets \>=100,000/mcL without platelet transfusion support within 2 weeks prior to screening.
- Hemoglobin \>=9 grams/deciliter (g/dL) without transfusion or growth factor (recombinant erythropoietin) within 2 weeks of screening.
- Serum creatinine less than or equal to (\<=)1.5 times (\*) upper limit of normal (ULN) or calculated creatinine clearance \>=50 milliliter per minute (mL/min) using Cockcroft-Gault equation.
- Total bilirubin \<=1.5\* ULN, except in participants with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll if direct bilirubin is \<=1.5\* ULN.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=2.5\* ULN, unless liver metastases are present, in which case they must be \<=5\* ULN.
- International normalized ratio or prothrombin time (PT) \<=1.5\* ULN unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants.
- Activated partial thromboplastin time (aPTT) \<=1.5\* ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Participant with known lupus anticoagulant and elevated PTT may be eligible on a case-by-case basis after discussion with the Sponsor's Medical Monitor.
- +20 more criteria
You may not qualify if:
- Participant has not recovered (i.e., to Grade \<=1 or to Baseline) from prior chemotherapy-induced adverse events (AEs).
- Participant has a known diagnosis of immunodeficiency or is receiving systemic steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Participant is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment.
- Participant has received prior systemic anticancer therapy including cytotoxic chemotherapy, PARP inhibitor, immune checkpoint inhibitors, hormonal therapy given with the intention to treat cancer, or biological therapy within 3 weeks of the first dose of study treatment. This washout period is required to ensure prior therapy is not confounding the toxicity profile of the investigational study drug or study drug combinations in cohorts.
- Participant has received live vaccine within 14 days of planned start of study therapy.
- Participant has symptomatic uncontrolled brain or leptomeningeal metastases. Participant who has untreated brain metastases and who is not symptomatic may enroll if the Investigator feels that treatment of these metastases is not indicated. A scan to confirm the absence of brain metastases is not required. Participant with spinal cord compression may be considered if she has received definitive treatment for this and evidence of clinically stable disease (SD) for 28 days prior to the first dose of study treatment.
- Participant had major surgery within 4 weeks of starting the study or participant has not recovered from any effects of any major surgery.
- Participant has a known additional malignancy that progressed or required active treatment within the last 2 years because reoccurrence of another malignancy would confound interpretation of ORR by RECIST v1.1 criteria. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer that is considered to be low risk for progression by the investigator.
- Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. These include, but are not limited to, Coronavirus disease 2019 (COVID-19), significant cardiovascular disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, and any psychiatric disorder that prohibits obtaining informed consent.
- Participant has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, might interfere with the participant's participation for the full duration of the study treatment, or is not in the best interest of the participant to participate.
- Participant has known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus ribonucleic acid \[qualitative\] is detected).
- Participant has known hypersensitivity to TSR-042, bevacizumab, niraparib, their components, or their excipients.
- Participant has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Participant has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., 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-PD-1 or anti-PD-L1 agent.
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Tesaro, Inc.lead
Study Sites (28)
GSK Investigational Site
Birmingham, Alabama, 35249, United States
GSK Investigational Site
Los Angeles, California, 90095, United States
GSK Investigational Site
San Francisco, California, 94109, United States
GSK Investigational Site
Stanford, California, 94304, United States
GSK Investigational Site
Ventura, California, 93003, United States
GSK Investigational Site
Tampa, Florida, 33606, United States
GSK Investigational Site
Chicago, Illinois, 60637, United States
GSK Investigational Site
Scarborough, Maine, 04074, United States
GSK Investigational Site
Baltimore, Maryland, 27710, United States
GSK Investigational Site
Boston, Massachusetts, 02114, United States
GSK Investigational Site
Boston, Massachusetts, 02215, United States
GSK Investigational Site
Rochester, Minnesota, 55905, United States
GSK Investigational Site
St Louis, Missouri, 63141, United States
GSK Investigational Site
New York, New York, 10029, United States
GSK Investigational Site
Rochester, New York, 14642, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73104, United States
GSK Investigational Site
Sioux Falls, South Dakota, 57105, United States
GSK Investigational Site
Houston, Texas, 77030, United States
GSK Investigational Site
Seattle, Washington, 98104, United States
GSK Investigational Site
Ottawa, Ontario, K1H 8L6, Canada
GSK Investigational Site
Montreal, Quebec, H2X 3E4, Canada
GSK Investigational Site
Montreal, Quebec, H4A 3J1, Canada
GSK Investigational Site
A Coruña, 15006, Spain
GSK Investigational Site
Madrid, 28027, Spain
GSK Investigational Site
Madrid, 28033, Spain
GSK Investigational Site
Madrid, 28050, Spain
GSK Investigational Site
Málaga, 29011, Spain
GSK Investigational Site
Pamplona, 31008, Spain
Related Publications (2)
Liu JF, Gaillard S, Wahner Hendrickson AE, Yeku O, Diver E, Gunderson Jackson C, Arend R, Ratner E, Samnotra V, Gupta D, Chung J, Zhang H, Compton N, Baines A, Bacque E, Liu X, Felicetti B, Konecny GE. Niraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial. JCO Precis Oncol. 2024 May;8:e2300693. doi: 10.1200/PO.23.00693.
PMID: 38754056DERIVEDBelotte J, Felicetti B, Baines AJ, YoussefAgha A, Rojas-Espaillat L, Ortiz AG, Provencher D, Vazquez RM, Cortijo LG, Zeng X. Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination-deficient stage III/IV ovarian cancer: study protocol for cohort C of the open-label, phase 2, randomized controlled multicenter OPAL trial. Trials. 2024 May 4;25(1):301. doi: 10.1186/s13063-024-08142-5.
PMID: 38702828DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- This is an open-label study
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 14, 2018
First Posted
July 2, 2018
Study Start
November 15, 2018
Primary Completion
June 28, 2024
Study Completion
March 31, 2025
Last Updated
July 15, 2025
Results First Posted
July 15, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will not share