Clinical trial NCT03955471: Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Participants With Platinum Resistant Ovarian Cancer
Official title: A Phase 2 Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Patients With Platinum-Resistant Ovarian Cancer (MOONSTONE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Neoplasms
Keywords: Open-label
Single-arm
Efficacy and Safety
Platinum-resistant ovarian cancer
Niraparib
dostarlimab
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gynecologic Oncology Group
First posted: 2019-05-20
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and dostarlimab (TSR-042) in participants with advanced, relapsed, high-grade ovarian, fallopian tube, endometrioid, clear cell ovarian or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease and who have also been previously treated with bevacizumab.


Eligibility criteria: Inclusion criteria:

* Participant must be female \>=18 years of age, able to understand the study procedures, and subsequently agreed to participate in the study by providing written informed consent.
* Participants must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer.
* Participants must be considered resistant to the last administered platinum therapy.
* Participants must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer.
* Participants must have been previously treated with platinum-based regimen, taxane agent(s), and bevacizumab.
* Participant has measurable disease according to RECIST v.1.1.
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Participant has adequate organ function.
* Females with childbearing potential have a serum pregnancy test that is negative 72 prior first dose and are not breastfeeding. Participant must also agree to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment.
* Participant must provide formalin fixed paraffin embedded (FFPE) tumor tissue block(s) with sufficient tumor content (as confirmed by the Sponsor's designated central laboratory) during screening to enable BRCA testing and PD-L1 testing. The use of slides created from paraffin-embedded tissue as opposed to FFPE blocks must be approved by the Sponsor.
* Participant must agree to complete health-related quality of life (HRQoL) questionnaires throughout the study.

Exclusion Criteria:

* Participant who experienced disease progression within 3 months (12 weeks or 84 days) of first-line platinum therapy.
* Participants with a known deleterious or suspected BRCA 1 or 2 mutation.
* Participant has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
* Participant has received prior therapy with a PARP-1/PARP-2 inhibitor.
* Participant has a known hypersensitivity to dostarlimab (TSR-042), Niraparib, their components, or their excipients.
* Participant has a known history of myelodysplastic syndrome or acute myeloid leukemia.
* Participant has not recovered from prior chemotherapy induced adverse events.
* 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, hormonal therapy given with the intention to treat ovarian cancer, or biological therapy within 3 weeks of the first dose of study treatment.
* Participant has received live vaccine within 14 days of planned start of study therapy
* Participant has symptomatic uncontrolled brain or leptomeningeal metastases. (If investigator feels participant symptoms are not symptomatic, participants can undergo a scan to confirm for eligibility).
* Participant had major surgery with 4 weeks of starting the first dose of the study treatment 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.
* Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active controlled infection.
* Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
* Participant has known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus ribonucleic acid, qualitative).
* Participant with a known history of human immunodeficiency virus (HIV) are allowed if they meet all of the following criteria:

  1. Cluster of differentiation 4 \>=350/microliter (μL) and viral load \<400 copies/milliliter (mL)
  2. No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment
  3. No history of HIV-associated malignancy for the past 5 years
  4. Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV started \>4 weeks prior to study enrollment
* Participant is immunocompromised. Participants with splenectomy are allowed.
* Participant has an ongoing bowel obstruction or has other conditions that would lead to impaired absorption of oral niraparib.
* 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.

Primary outcomes:
measure: Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC)
timeFrame: Up to approximately 22 months
measure: ORR in Participants With PROC Who Have Programmed Cell Death-ligand 1 (PD-L 1) Positive Status
timeFrame: Up to approximately 22 months
Secondary outcomes:
measure: Duration of Response (DOR) in Participants With PROC
timeFrame: Up to approximately 22 months
measure: DOR in Participants With PROC Who Have PD-L 1 Positive Status
timeFrame: Up to approximately 22 months
measure: Progression-free Survival (PFS) in Participants With PROC
timeFrame: Up to approximately 22 months
measure: PFS in Participants With PROC Who Have PD-L 1 Positive Status
timeFrame: Up to approximately 22 months
measure: Overall Survival (OS) in Participants With PROC
timeFrame: Up to approximately 22 months
measure: OS in Participants With PROC Who Have PD-L 1 Positive Status
timeFrame: Up to approximately 22 months
measure: Disease Control Rate (DCR) in Participants With PROC
timeFrame: Up to approximately 22 months
measure: DCR in Participants With PROC Who Have PD-L 1 Positive Status
timeFrame: Up to approximately 22 months
measure: ORR in Participants With PROC Based on Independent Review Committee (IRC) Assessment
timeFrame: Up to approximately 22 months
measure: ORR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
timeFrame: Up to approximately 22 months
measure: DOR in Participants With PROC Based on IRC Assessment
timeFrame: Up to approximately 22 months
measure: DOR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
timeFrame: Up to approximately 22 months
measure: PFS in Participants With PROC Based on IRC Assessment
timeFrame: Up to approximately 22 months
measure: PFS in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
timeFrame: Up to approximately 22 months
measure: DCR in Participants With PROC Based on IRC Assessment
timeFrame: Up to approximately 22 months
measure: DCR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
timeFrame: Up to approximately 22 months
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs) and Adverse Event of Special Interest (AESI)
timeFrame: Up to approximately 27 months
measure: Number of Participants With Grade Shift From Baseline in Hematology
timeFrame: Up to approximately 27 months
measure: Number of Participants With Grade Shift From Baseline in Plasma Chemistry
timeFrame: Up to approximately 27 months
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Up to approximately 27 months
measure: Change From Baseline in Pulse Rate
timeFrame: Up to approximately 27 months
measure: Change From Baseline in Temperature
timeFrame: Up to approximately 27 months
measure: Change From Baseline in Prothrombin International Normalized Ratio
timeFrame: Baseline and up to approximately 27 months
measure: Change in Baseline in Activated Partial Thromboplastin Time
timeFrame: Baseline and up to approximately 27 months
measure: Change From Baseline in Thyrotropin
timeFrame: Baseline and up to approximately 27 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Duarte
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Orange
country: United States
facility: GSK Investigational Site
state: California
city: Solvang
country: United States
facility: GSK Investigational Site
state: California
city: Deerfield Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Iowa City
country: United States
facility: GSK Investigational Site
state: Iowa
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Burlington
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Jackson
country: United States
facility: GSK Investigational Site
state: Mississippi
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Eugene
country: United States
facility: GSK Investigational Site
state: Oregon
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Chattanooga
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Germantown
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: