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Study of Niraparib Administered Alone and in Combination With PD-1 Inhibitor in Patients With Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03308942
Recruitment Status : Active, not recruiting
First Posted : October 13, 2017
Last Update Posted : January 14, 2020
Sponsor:
Collaborators:
Covance
Myriad Genetics, Inc.
NeoGenomics Laboratories
DrugDev
Resolution Bioscience
Syneos Health
Almac Group
imedidata
Information provided by (Responsible Party):
Tesaro, Inc.

Tracking Information
First Submitted Date  ICMJE October 3, 2017
First Posted Date  ICMJE October 13, 2017
Last Update Posted Date January 14, 2020
Actual Study Start Date  ICMJE November 14, 2017
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 30, 2018)
  • Objective Response Rate in patients with NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score >= 50%) [ Time Frame: Stage 1 6-8 months ]
    Proportion of patients with the confirmed overall response of complete response or partial response
  • Objective Response Rate in patients with NSCLC whose tumors express PD-L1 (Tumor Proportion Score 1-49%) [ Time Frame: Stage 1 6-8 months ]
    Proportion of patients with the confirmed overall response of complete response or partial response
Original Primary Outcome Measures  ICMJE
 (submitted: October 9, 2017)
  • Objective Response Rate in patients with NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score >= 50%) [ Time Frame: Stage 1 6-8 months ]
    Proportion of patients with the confirmed overall response of complete response or partial response
  • Objective Response Rate in patients with NSCLC whose tumors express PD-L1 (Tumor Proportion Score 1-49%) [ Time Frame: Stage 1 6-8 months ]
    Proportion of patients with the confirmed overall response of complete response or partial response
  • Objective Response Rate in patients with squamous NSCLC [ Time Frame: Stage 1 6-8 months ]
    Proportion of patients with the confirmed overall response of complete response or partial response
Change History Complete list of historical versions of study NCT03308942 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2017)
  • Treatment emergent adverse events, serious adverse events, assessment of clinical laboratory values [ Time Frame: Stage 1 6-8 months ]
    Assessed by CTCAE v4.03
  • Duration of response [ Time Frame: Stage 1 6-8 months ]
    Time from first documented complete response or partial response until the subsequent documented disease progression or death
  • Overall survival [ Time Frame: Stage 1 6-8 months ]
    Time from date of first dose to date of death
  • Disease control rate [ Time Frame: Stage 1 6-8 months ]
    Proportion of patients with best overall response of complete response, partial response, or stable disease
  • Progression free survival [ Time Frame: Stage 1 6-8 months ]
    Time from date of first dose to date of disease progression or death
  • Pharmacokinetic parameter: area under the curve of niraparib [ Time Frame: Stage 1 6-8 months ]
  • Pharmacokinetic parameter: maximum concentration of niraparib [ Time Frame: Stage 1 6-8 months ]
  • Pharmacokinetic parameter: maximum concentration at steady state of niraparib [ Time Frame: Stage 1 6-8 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Niraparib Administered Alone and in Combination With PD-1 Inhibitor in Patients With Non-Small Cell Lung Cancer
Official Title  ICMJE Phase 2, Multi-Arm Study of Niraparib Administered Alone and in Combination With PD-1 Inhibitor in Patients With Non-Small Cell Lung Cancer
Brief Summary A phase 2 study to evaluate the efficacy of niraparib alone and in combination with PD-1 inhibitor in three cohorts: all histologies with high PD-L1 expression (greater than 50% TPS), all histologies low PD-L1 expression (1-49% TPS), and squamous cell lung cancer. [TPS=Tumor Proportion Score]
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Neoplasms
Intervention  ICMJE
  • Drug: Niraparib
    PARP inhibitor, Capsule, 200mg dose, QD
    Other Name: Zejula
  • Biological: PD-1 Inhibitor
    Monoclonal antibody, IV administration
Study Arms  ICMJE
  • Experimental: NSCLC High PD-L1 Expressing
    All Non-small cell lung cancer histologies with a high expression of PD-L1 as defined as TPS greater or equal to 50%. Treated with combination of niraparib and PD-1 Inhibitor.
    Interventions:
    • Drug: Niraparib
    • Biological: PD-1 Inhibitor
  • Experimental: NSCLC Low PD-L1 Expressing
    All Non-small cell lung cancer histologies with a low expression of PD-L1 as defined as TPS 1-49%. Treated with combination of niraparib and PD-1 Inhibitor.
    Interventions:
    • Drug: Niraparib
    • Biological: PD-1 Inhibitor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 30, 2018)
142
Original Estimated Enrollment  ICMJE
 (submitted: October 9, 2017)
136
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

General Inclusion Criteria:

  1. Male or female at least 18 years of age
  2. Histological or cytological proven advanced (unresectable) or metastatic NSCLC as defined as stage IIIB (positive supraclavicular lymph nodes) not amenable to definitive chemoradiotherapy or stage IV NSCLC
  3. Measurable disease by RECIST v1.1
  4. ECOG performance status of 0 to 1
  5. Adequate organ function, defined as (Note: CBC test should be obtained without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample):

    1. Absolute neutrophil count (ANC) ≥ 1500/µL
    2. Platelets ≥ 100,000/µL
    3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
    4. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional ULN
    5. Total bilirubin ≤ 1.5 × ULN except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct bilirubin.
    6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN unless liver metastases are present, in which case they must be ≤ 5× ULN
  6. Patient must have recovered to Grade 1 toxicity from prior cancer therapy (a patient with Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may qualify for this study).
  7. Provision of (archival or fresh) FFPE tumor tissue.
  8. Able to take oral medications
  9. Female patient has a negative serum pregnancy test within 72 hours prior to taking study drug if of childbearing potential, and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment, or be of non-childbearing potential.
  10. Male patient agrees to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  11. Able to understand the study procedures and agree to participate in the study by providing written informed consent

Cohort Specific Inclusion Criteria:

  1. Cohorts 1 and 1A (combination of niraparib and PD-1 inhibitor): patients must have tumors with high PD-L1 expression (TPS ≥ 50%) per local assessment; with no known EGFR-sensitizing mutation and/or ROS-1 or ALK translocations, and no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment for metastatic NSCLC
  2. Cohorts 2 and 2A (combination of niraparib and PD-1 inhibitor): patients must have tumors with PD-L1 expression (TPS between 1% and 49%) per local assessment, with no known EGFR-sensitizing mutation and/or ROS-1 or ALK translocation, and no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment for metastatic NSCLC

Cohorts 1, 1A, 2 and 2A Exclusion Criteria:

  1. Has received systemic therapy for the treatment of advanced stage NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease
  2. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  3. Known hypersensitivity to the components of niraparib, PD-1 inhibitor, or their excipients
  4. Known EGFR (exon 19 and 21) mutations, ALK translocations, and/or ROS-1 translocations
  5. Condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
  6. Known diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  7. Immunocompromised patient (Note: patients with splenectomy are allowed)
  8. Current participation in a treatment study or past participation in a study of an investigational agent within 4 weeks before the first dose of study treatment
  9. Symptomatic uncontrolled brain or leptomeningeal metastases
  10. Active autoimmune disease that 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, etc.) is not considered a form of systemic treatment
  11. Major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery
  12. Other active concomitant malignancy that warrants systemic therapy
  13. Poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, uncontrolled hypertension, or any psychiatric disorder that prohibits obtaining informed consent
  14. Known interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis requiring steroid treatment
  15. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and for 180 days (for pregnancy or conception) or 30 days (for breastfeeding) after the last dose of study treatment
  16. Male patient is expecting to donate sperm or father children while receiving study drug or for 120 days after the last dose of study treatment
  17. Known active hepatic disease (known hepatic cirrhosis, hepatitis B surface antigen positive status, or suspected active hepatitis C infection)
  18. Prior treatment with a known poly (ADP-ribose) polymerase (PARP) inhibitor
  19. Patient who received a live vaccine within 30 days of planned start of study therapy
  20. Known history of MDS or AML
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03308942
Other Study ID Numbers  ICMJE 3000-02-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Tesaro, Inc.
Study Sponsor  ICMJE Tesaro, Inc.
Collaborators  ICMJE
  • Covance
  • Myriad Genetics, Inc.
  • NeoGenomics Laboratories
  • DrugDev
  • Resolution Bioscience
  • Syneos Health
  • Almac Group
  • imedidata
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account Tesaro, Inc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP