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

• ClinicalTrials.gov Identifier: NCT03308942
• Recruitment Status: Active, not recruiting
• First Posted: October 13, 2017
• Last Update Posted: October 28, 2019
• Sponsor: Tesaro, Inc.
• Collaborators: Covance; Myriad Genetics, Inc.; NeoGenomics Laboratories; DrugDev; Resolution Bioscience; Syneos Health; Almac Group; imedidata
• Information provided by (Responsible Party): Tesaro, Inc.

Study Description

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]

Condition or disease	Intervention/treatment	Phase
Lung Neoplasms	Drug: Niraparib; Biological: PD-1 Inhibitor	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 142 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 14, 2017
• Estimated Primary Completion Date: September 2021
• Estimated Study Completion Date: January 2022

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Niraparib; PARP inhibitor, Capsule, 200mg dose, QD; Other Name: Zejula; Biological: PD-1 Inhibitor; Monoclonal antibody, IV administration
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.	Drug: Niraparib; PARP inhibitor, Capsule, 200mg dose, QD; Other Name: Zejula; Biological: PD-1 Inhibitor; Monoclonal antibody, IV administration

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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

Secondary Outcome Measures :

1. Treatment emergent adverse events, serious adverse events, assessment of clinical laboratory values [ Time Frame: Stage 1 6-8 months ]
   Assessed by CTCAE v4.03
2. 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
3. Overall survival [ Time Frame: Stage 1 6-8 months ]
   Time from date of first dose to date of death
4. 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
5. Progression free survival [ Time Frame: Stage 1 6-8 months ]
   Time from date of first dose to date of disease progression or death
6. Pharmacokinetic parameter: area under the curve of niraparib [ Time Frame: Stage 1 6-8 months ]
7. Pharmacokinetic parameter: maximum concentration of niraparib [ Time Frame: Stage 1 6-8 months ]
8. Pharmacokinetic parameter: maximum concentration at steady state of niraparib [ Time Frame: Stage 1 6-8 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
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

Contacts and Locations

Locations

United States, California

Innovative Clinical Research Institute

Whittier, California, United States, 90603

United States, Florida

Sylvester Comprehensive Cancer Center at U. of Miami

Miami, Florida, United States, 33136

Hematology Oncology Assoc of the Treasure Coast

Port Saint Lucie, Florida, United States, 34952

United States, Georgia

Emory University - Winship Cancer Institute

Atlanta, Georgia, United States, 30322

United States, Illinois

Ingalls Memorial Hospital

Harvey, Illinois, United States, 60426

Healthcare Research Network III

Tinley Park, Illinois, United States, 60487

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02115

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

United States, Ohio

University Hospitals Case Medical Center

Cleveland, Ohio, United States, 44106

United States, Tennessee

Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Washington

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, United States, 99336

Nortwest Medical Specialists

Tacoma, Washington, United States, 98405

Sponsors and Collaborators

Tesaro, Inc.

Covance

Myriad Genetics, Inc.

NeoGenomics Laboratories

DrugDev

Resolution Bioscience

Syneos Health

Almac Group

imedidata

Investigators

• Study Director: Iryna Teslenko, M.D.; Tesaro Inc., a GSK Company

More Information

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT03308942 History of Changes
• Other Study ID Numbers: 3000-02-001
• First Posted: October 13, 2017
• Last Update Posted: October 28, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tesaro, Inc.:

Niraparib; Zejula; PARP Inhibitor; PD-1 Inhibitor

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Niraparib; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents