Effects of Single Agent Niraparib and Niraparib Plus Programmed Cell Death-1 (PD-1) Inhibitors in Non-Small Cell Lung Cancer Participants

NCT03308942 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2133523000-02-001
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 16

Brief Summary

This is a multicenter, open-label, phase 2 study to evaluate the efficacy and safety of niraparib alone and in combination with PD-1 inhibitors in participants with locally advanced and metastatic non-small cell lung cancer (NSCLC). The study will consist of 2 stages. In stage 1, participants from Cohorts 1 and 2 will receive niraparib plus PD-1 inhibitor; pembrolizumab and participants from Cohort 3 will receive niraparib alone. In Stage 2, participants from Cohorts 1A and 2A will receive niraparib plus the PD-1 inhibitor, TSR-042 (Dostarlimab).

Conditions

Neoplasms

Keywords

Niraparib; NSCLC; Pembrolizumab; Dostarlimab; TSR-042

Outcome Measures

Primary Outcomes (4)

• Stage 1: Cohort 1: Objective Response Rate (ORR)

  ORR is the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis. PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Data has been presented for participants with NSCLC whose tumors have high PD-L1 expression (TPS\>=50%). Confidence interval was calculated using binomial exact method.

  Up to a maximum of 29 months

• Stage 1: Cohort 2: Objective Response Rate

  ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per RECIST v1.1. Data has been presented for participants with NSCLC having PD-L1 expression in tumors (TPS: 1 to 49%). Confidence interval was calculated using binomial exact method.

  Up to a maximum of 17 months

• Stage 1: Cohort 3: Objective Response Rate

  ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per RECIST v1.1. Data is presented for participants with locally advanced and metastatic squamous NSCLC. Confidence interval was calculated using binomial exact method.

  Up to a maximum of 6 months

• Stage 2: Cohort 1A and Cohort 2A: Objective Response Rate

  ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per RECIST v1.1. Confidence interval was calculated using binomial exact method.

  Up to a maximum of 17 months

Secondary Outcomes (24)

• Stage 1: Cohort 1: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

  Up to a maximum of 45 months

• Stage 1: Cohort 2: Number of Participants With Non-SAEs and SAEs

  Up to a maximum of 17 months

• Stage 1: Cohort 3: Number of Participants With Non-SAEs and SAEs

  Up to a maximum of 6 months

• Stage 2: Cohorts 1A and 2A: Number of Participants With Non-SAEs and SAEs

  Up to a maximum of 29 months

• Stage 1: Cohort 1: Number of Participants Discontinuing the Study Due to AEs

  Up to a maximum of 45 months

Other Outcomes (4)

• Stage 1: Cohort 1: Overall Survival (OS)

  Up to a maximum of 45 months

• Stage 1: Cohort 2: Overall Survival

  Up to a maximum of 17 months

• Stage 1: Cohort 3: Overall Survival

  Up to a maximum of 6 months

Study Arms (5)

Stage 1 (Cohort 1): Niraparib plus Pembrolizumab

EXPERIMENTAL

Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/programmed death-ligand 1 (PD-L1) inhibitor treatment and whose tumors have high PD-L1 expression (tumor proportion score \[TPS\]: \>= 50 percent \[%\]) will receive combination of niraparib and a PD-1 inhibitor; pembrolizumab.

Drug: Niraparib; Biological: Pembrolizumab

Stage 1 (Cohort 2): Niraparib plus Pembrolizumab

EXPERIMENTAL

Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have PD-L1 expression (TPS: 1% to 49%) will receive combination of niraparib and a PD-1 inhibitor; pembrolizumab.

Drug: Niraparib; Biological: Pembrolizumab

Stage 1 (Cohort 3): Niraparib

EXPERIMENTAL

Participants with locally advanced and metastatic squamous NSCLC who have been previously treated with both platinum and either PD-1 or PD-L1 inhibitor will receive single agent niraparib.

Drug: Niraparib

Stage 2 (Cohort 1A): Niraparib plus TSR-042 (Dostarlimab)

EXPERIMENTAL

Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have high PD-L1 expression (TPS: \>= 50%) will receive combination of niraparib and a PD-1 inhibitor; TSR-042 (Dostarlimab).

Drug: Niraparib; Biological: TSR-042 (Dostarlimab)

Stage 2 (Cohort 2A): Niraparib plus TSR-042 (Dostarlimab)

EXPERIMENTAL

Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have PD-L1 expression (TPS: 1% to 49%) will receive combination of niraparib and a PD-1 inhibitor; TSR-042 (Dostarlimab).

Drug: Niraparib; Biological: TSR-042 (Dostarlimab)

Interventions

Niraparib DRUG

Niraparib is an orally available, potent, highly selective poly adenosine diphosphate- ribose (poly ADP-ribose) polymerase-1 (PARP-1) and PARP-2 inhibitor. It will be available as 100 milligrams (mg) capsules and will be administered as 2 X 100 mg capsules (200 mg per day) orally once daily (QD).

Stage 1 (Cohort 1): Niraparib plus Pembrolizumab; Stage 1 (Cohort 2): Niraparib plus Pembrolizumab; Stage 1 (Cohort 3): Niraparib; Stage 2 (Cohort 1A): Niraparib plus TSR-042 (Dostarlimab); Stage 2 (Cohort 2A): Niraparib plus TSR-042 (Dostarlimab)

Pembrolizumab BIOLOGICAL

Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G-4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands (PD-L1 and PD-L2). It will be available as 50 mg lyophilized powder single-use vials or 100 mg/4 milliliters (mL) (25 mg/mL) solution in a single-dose vial. It will be administered at a dose of 200 mg intravenous (IV) using a 30-minute IV infusion

Stage 1 (Cohort 1): Niraparib plus Pembrolizumab; Stage 1 (Cohort 2): Niraparib plus Pembrolizumab

TSR-042 (Dostarlimab) BIOLOGICAL

TSR-042 (Dostarlimab) is a humanized mAb of the IgG4/kappa isotype that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. It will be administered at a dose of 500 mg for every 3 weeks (Q3W) for first 4 cycles followed by 1000 mg for every 6 weeks (Q6W) for all subsequent cycles using a 30-minute IV infusion. TSR-042 (dostarlimab) will be supplied as a solution of 160 mg (20 mg/mL) or 500 mg (50 mg/mL) in a single-dose vial.

Stage 2 (Cohort 1A): Niraparib plus TSR-042 (Dostarlimab); Stage 2 (Cohort 2A): Niraparib plus TSR-042 (Dostarlimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants at least 18 years of age.
• 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.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Adequate organ function, defined as:
• Absolute neutrophil count (ANC) \>= 1500 per microliter (/µL).
• Platelets \>= 100,000/µL.
• Hemoglobin \>= 9 grams per deciliter (g/dL) or \>= 5.6 millimoles per liter (mmol/L).
• Serum creatinine \<= 1.5 times upper limit of normal (ULN) or creatinine clearance \>= 50 milliliters per minute (mL/min) (as calculated using the Cockcroft Gault equation or measured using 24-hour urine creatinine clearance) for participants with creatinine levels \> 1.5 times institutional ULN.
• Total bilirubin \<= 1.5 times ULN except in participants with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll if direct bilirubin \<= 1.5 times ULN of the direct bilirubin.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 2.5 times ULN unless liver metastases are present, in which case they must be \<= 5 times ULN.
• Participant must have recovered to Grade 1 toxicity from prior cancer therapy (a participant with Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may qualify for this study).
• Participant agrees to submit formalin fixed paraffin embedded (FFPE) tumor tissue specimen, which may have been collected at any time prior to screening. If no archival FFPE tumor tissue is available, participant agrees to undergo a tumor tissue biopsy before Cycle 1/Day 1. (For Cohort 3 only: if diagnosis was made by cytology and archival tissue is not available, participant will not need to provide tumor tissue).
• Participants is able to take oral medications.
• Female participant meets the following criteria:

You may not qualify if:

• Participant 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.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Known hypersensitivity to the components of niraparib, pembrolizumab, TSR-042 (Dostarlimab), or their excipients.
• Known EGFR (exon 19 and 21) mutations, ALK translocations, and/or ROS-1 translocations.
• Participant has a history or current condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the participant's participation for the full duration of the study treatment.
• Known diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Participant is immunocompromised, in the opinion of the Investigator.
• 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.
• Symptomatic uncontrolled brain or leptomeningeal metastases. (To be considered "controlled," central nervous system \[CNS\] disease must have undergone treatment \[example, radiation or chemotherapy\] at least 1 month prior to study entry. The participant must not have any new or progressive signs or symptoms related to the CNS disease and must be taking \<= 10 mg of prednisone or equivalent per day or no steroids.) Participants who have untreated brain metastases and who are 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. Participants with spinal cord compression may be considered if they have received definitive treatment for this and evidence of clinically SD for 28 days.
• Active autoimmune disease that required systemic treatment in the past 2 years (with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (examples, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Major surgery within 3 weeks of starting the study or participant has not recovered from any effects of any major surgery.
• Other active concomitant malignancy that warrants systemic therapy.
• 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, active uncontrolled coagulopathy or any psychiatric disorder that prohibits obtaining informed consent.
• Known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis requiring steroid treatment.
• Participant 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.

Sponsors & Collaborators

• Tesaro, Inc.: lead

Study Sites (16)

GSK Investigational Site

Whittier, Alaska, 90603, United States

Location

GSK Investigational Site

Port Saint Lucie, Florida, 34952, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30322, United States

Location

GSK Investigational Site

Harvey, Illinois, 60426, United States

Location

GSK Investigational Site

Tinley Park, Illinois, 60487, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

Florham Park, New Jersey, 07932, United States

Location

GSK Investigational Site

Buffalo, New York, 14263, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Canton, Ohio, 44718, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Columbus, Ohio, 31904, United States

Location

GSK Investigational Site

Toledo, Ohio, 43623, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Kennewick, Washington, 99336, United States

Location

GSK Investigational Site

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• Ramalingam SS, Thara E, Awad MM, Dowlati A, Haque B, Stinchcombe TE, Dy GK, Spigel DR, Lu S, Iyer Singh N, Tang Y, Teslenko I, Iannotti N. JASPER: Phase 2 trial of first-line niraparib plus pembrolizumab in patients with advanced non-small cell lung cancer. Cancer. 2022 Jan 1;128(1):65-74. doi: 10.1002/cncr.33885. Epub 2021 Sep 3.

  PMID: 34478166 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

niraparib; pembrolizumab; dostarlimab

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This will be an open-label study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will receive niraparib either as monotherapy or in combination with pembrolizumab during Stage 1 of the study. Participants will receive niraparib in combination with TSR-042 (dostarlimab) during Stage 2 of the study.

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: October 13, 2017
• Study Start: September 29, 2017
• Primary Completion: May 4, 2020
• Study Completion: August 31, 2021
• Last Updated: October 16, 2023
• Results First Posted: July 7, 2021

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

US (16)