Clinical Trials /

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

NCT03308942

Description:

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]

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2, Multi-Arm Study of Niraparib Administered Alone and in Combination With PD-1 Inhibitor in Patients With Non-Small Cell Lung Cancer
  • Official Title: Phase 2, Multi-Arm Study of Niraparib Administered Alone and in Combination With PD-1 Inhibitor in Patients With Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 3000-02-001
  • NCT ID: NCT03308942

Conditions

  • Lung Neoplasms

Interventions

DrugSynonymsArms
NiraparibZejulaNSCLC High PD-L1 Expressing
PD-1 InhibitorNSCLC High PD-L1 Expressing

Purpose

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]

Trial Arms

NameTypeDescriptionInterventions
NSCLC High PD-L1 ExpressingExperimentalAll 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.
  • Niraparib
NSCLC Low PD-L1 ExpressingExperimentalAll 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.
  • Niraparib
Squamous NSCLCExperimentalSquamous non-small cell lung cancer. Treated with niraparib monotherapy.
  • Niraparib

Eligibility Criteria

        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

               7. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN unless
                  patient is receiving anticoagulant therapy as long as PT or partial
                  thromboplastin time (PTT) is within therapeutic range of intended use of
                  anticoagulants

               8. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless patient is
                  receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
                  of intended use

          6. Provision of (archival or fresh) FFPE tumor tissue. (For Cohort 3 only: if diagnosis
             was made by cytology and archival tissue is not available, patient will not need to
             provide tumor tissue)

          7. Able to take oral medications

          8. 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.

          9. 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.

         10. Able to understand the study procedures and agree to participate in the study by
             providing written informed consent

        Cohort Specific Inclusion Criteria:

          1. Cohort 1 (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. Cohort 2 (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

          3. Cohort 3 (single agent niraparib): patients must have metastatic sqNSCLC and have
             progressed after both prior platinum-based chemotherapy and prior PD-1 or PD-L1
             inhibitor treatment

        Cohorts 1 and 2 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. Patients who
             received colony stimulating factors (eg, granulocyte colony-stimulating factor
             [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant
             erythropoietin) within 2 weeks prior to the first dose of study treatment are not
             eligible

          6. Has not recovered (ie, to ≤ Grade 1 or to baseline) from chemotherapy induced AEs.
             Note: Patient with ≤ Grade 1 neuropathy or ≤ Grade 2 alopecia is an exception to this
             criterion and may qualify for the study. Persistent > Grade 2 toxicity from prior
             cancer therapy

          7. 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

          8. Immunocompromised patient (Note: patients with splenectomy are allowed)

          9. 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

         10. Symptomatic uncontrolled brain or leptomeningeal metastases

         11. 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

         12. Major surgery within 3 weeks of starting the study or patient has not recovered from
             any effects of any major surgery

         13. Other active concomitant malignancy that warrants systemic therapy

         14. 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

         15. Has received a transfusion (platelets or red blood cells) within 3 weeks before the
             first dose of niraparib

         16. Known interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis
             requiring steroid treatment

         17. Patient is pregnant, breastfeeding, or expecting to conceive children, while receiving
             study treatment and for 3 months after the last dose of study treatment

         18. Known active hepatic disease (known hepatic cirrhosis, hepatitis B surface antigen
             positive status, or suspected active hepatitis C infection)

         19. Prior treatment with a known poly (ADP-ribose) polymerase (PARP) inhibitor

         20. Patient who received a live vaccine within 30 days of planned start of study therapy

         21. Known history of MDS or AML

        Cohort 3 Exclusion Criteria:

          1. Platinum-treated patient that progressed while on or within less than 8 weeks from the
             last day of platinum administration

          2. Known hypersensitivity to the components of niraparib or excipients

          3. 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. Patients who
             received colony stimulating factors (eg, G-CSF, GM-CSF or recombinant erythropoietin)
             within 2 weeks prior to the first dose of study treatment are not eligible

          4. Has not recovered (ie, to ≤ Grade 1 or to baseline) from chemotherapy induced AEs.
             Note: Patient with ≤ Grade 1 neuropathy or ≤ Grade 2 alopecia is an exception to this
             criterion and may qualify for the study. Persistent > Grade 2 toxicity from prior
             cancer therapy

          5. 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

          6. 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

          7. Symptomatic uncontrolled brain or leptomeningeal metastases.

          8. Major surgery within 3 weeks of starting the study or patient has not recovered from
             any effects of any major surgery

          9. Other active concomitant malignancy that warrants systemic therapy

         10. 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

         11. Has received a transfusion (platelets or red blood cells) within 3 weeks of the first
             dose of niraparib

         12. Patient is pregnant, breastfeeding, or expecting to conceive children, while receiving
             study treatment and for 3 months after the last dose of study treatment

         13. Immunocompromised patient (Note: patients with splenectomy are allowed)

         14. Known active hepatic disease (known hepatic cirrhosis, hepatitis B surface antigen
             positive status, or suspected active hepatitis C infection)

         15. Prior treatment with a known poly (ADP-ribose) polymerases (PARP) inhibitor

         16. Patient who received a live vaccine within 30 days of planned start of study therapy

         17. Known history of MDS or AML
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Proportion of patients with the confirmed overall response of complete response or partial response

Secondary Outcome Measures

Measure:Treatment emergent adverse events, serious adverse events, assessment of clinical laboratory values
Time Frame:Stage 1 6-8 months
Safety Issue:
Description:Assessed by CTCAE v4.03
Measure:Duration of response
Time Frame:Stage 1 6-8 months
Safety Issue:
Description:Time from first documented complete response or partial response until the subsequent documented disease progression or death
Measure:Overall survival
Time Frame:Stage 1 6-8 months
Safety Issue:
Description:Time from date of first dose to date of death
Measure:Disease control rate
Time Frame:Stage 1 6-8 months
Safety Issue:
Description:Proportion of patients with best overall response of complete response, partial response, or stable disease
Measure:Progression free survival
Time Frame:Stage 1 6-8 months
Safety Issue:
Description:Time from date of first dose to date of disease progression or death
Measure:Pharmacokinetic parameter: area under the curve of niraparib
Time Frame:Stage 1 6-8 months
Safety Issue:
Description:
Measure:Pharmacokinetic parameter: maximum concentration of niraparib
Time Frame:Stage 1 6-8 months
Safety Issue:
Description:
Measure:Pharmacokinetic parameter: maximum concentration at steady state of niraparib
Time Frame:Stage 1 6-8 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tesaro, Inc.

Trial Keywords

  • Niraparib
  • Zejula
  • PARP Inhibitor
  • PD-1 Inhibitor

Last Updated

October 9, 2017