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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04475939




Registration number
NCT04475939
Ethics application status
Date submitted
14/07/2020
Date registered
17/07/2020
Date last updated
5/02/2024

Titles & IDs
Public title
Placebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants With Advanced/Metastatic Non-small Cell Lung Cancer
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants Whose Disease Has Remained Stable or Responded to First-Line Platinum Based Chemotherapy With Pembrolizumab for Stage IIIB/IIIC or IV Non-Small Cell Lung Cancer (ZEAL-1L)
Secondary ID [1] 0 0
213400
Universal Trial Number (UTN)
Trial acronym
ZEAL-1L
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Cancer, Non-Small Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Niraparib
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Placebo

Experimental: Participants receiving niraparib plus pembrolizumab - Eligible participants will receive niraparib along with pembrolizumab.

Placebo comparator: Participants receiving placebo plus pembrolizumab - Eligible participants will receive matching placebo along with pembrolizumab.


Treatment: Drugs: Niraparib
Niraparib will be administered

Treatment: Drugs: Pembrolizumab
Pembrolizumab will be administered

Treatment: Drugs: Placebo
Matching placebo will be administered
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 in overall population
Timepoint [1] 0 0
Up to approximately 3 years
Primary outcome [2] 0 0
Overall survival (OS) in overall population
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [1] 0 0
PFS assessed by BICR using RECIST v 1.1 in non-squamous histology (NSQ) population
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [2] 0 0
PFS assessed by BICR using RECIST v 1.1 in complete and partial response (CR/PR) population
Timepoint [2] 0 0
Up to approximately 3 years
Secondary outcome [3] 0 0
OS in NSQ population
Timepoint [3] 0 0
Up to approximately 5 years
Secondary outcome [4] 0 0
OS in CR/PR population
Timepoint [4] 0 0
Up to approximately 5 years
Secondary outcome [5] 0 0
Time to progression (TTP)
Timepoint [5] 0 0
Up to approximately 3 years
Secondary outcome [6] 0 0
PFS by investigator assessment using RECIST v1.1
Timepoint [6] 0 0
Up to approximately 3 years
Secondary outcome [7] 0 0
CNS PFS as assessed by BICR using RANO-BM
Timepoint [7] 0 0
Up to approximately 3 years
Secondary outcome [8] 0 0
PFS as assessed by BICR using RECIST v1.1 by programmed cell death-ligand 1 (PD-L1) status
Timepoint [8] 0 0
Up to approximately 3 years
Secondary outcome [9] 0 0
OS by PD-L1 status
Timepoint [9] 0 0
Up to approximately 5 years
Secondary outcome [10] 0 0
Time to Deterioration (TTD) in Lung Symptoms
Timepoint [10] 0 0
Up to approximately 3 years
Secondary outcome [11] 0 0
Change from Baseline in Health-related quality of life (HRQoL) and symptoms by EORTC QLQ-C30-item Core module (EORTC QLQ-C30) (Scores on a scale)
Timepoint [11] 0 0
Baseline, Day 1 in Cycles 1, 2, 3, 4, 5 (Each cycle is of 21 Days); thereafter every 2 cycles until 90 days after last treatment dose (up to approximately 3 years)
Secondary outcome [12] 0 0
Change from Baseline in HRQoL and symptoms by EORTC QLQ-LC13 (Scores on a scale)
Timepoint [12] 0 0
Baseline, Day 1 in Cycles 1, 2, 3, 4, 5 (Each cycle is of 21 Days); thereafter every 2 cycles until 90 days after last treatment dose (up to approximately 3 years)
Secondary outcome [13] 0 0
Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)
Timepoint [13] 0 0
Up to approximately 3 years
Secondary outcome [14] 0 0
Plasma concentrations of niraparib
Timepoint [14] 0 0
Up to approximately 3 years

Eligibility
Key inclusion criteria
Inclusion criteria:

* Participant must be >=18 years of age.
* Has a histologically or cytologically confirmed diagnosis of NSCLC without known targetable driver alteration (either non-squamous or squamous histology; mixed histology is allowed for which an approved targeted therapy is available in the 1L induction/maintenance therapy setting).
* Has advanced (Stage IIIB or Stage IIIC, not amenable to definitive chemoradiotherapy) or metastatic (Stage IV) or metastatic (Stage IV) NSCLC.
* Has completed at least 4 but no more than 6 cycles of standard of care first-line platinum-based induction chemotherapy with pembrolizumab.
* Has SD, PR, or CR of the NSCLC per Investigator's assessment after completion of 4 to 6 cycles of standard of care first-line platinum-based induction chemotherapy with pembrolizumab.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Has a life expectancy of at least 12 weeks.
* Has adequate organ and bone marrow function.
* Must submit tumor specimens.
* Must be able to swallow and retain orally administered study treatment.
* A female is eligible to participate if she is not pregnant or breastfeeding, and must follow contraceptive guidance during the treatment period and 180 days afterwards.
* A male is eligible to participate if he agrees to contraceptive guidance and refrains from sperm donation during the intervention period and for at least 90 days after the last dose of study treatment.
* Is able to understand the study procedures and agrees to participate in the study by providing written informed consent. Participants must be informed that their participation is voluntary. Participants will be required to sign a statement of informed consent to participate in the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Has mixed small cell lung cancer or sarcomatoid variant NSCLC.
* Has received prior Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor(s) in prior lines of treatment.
* Has systolic blood pressure (BP) >140 millimeters of mercury (mmHg) or diastolic BP >90 mmHg.
* Has any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
* Has leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiographic signs of CNS hemorrhage.
* Has received colony-stimulating factors (granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 4 weeks prior to the first dose of study treatment.
* Has an active or previously documented autoimmune or inflammatory disorder.
* Is receiving chronic systemic steroids (prednisone >20 mg per day) other than intermittent use of bronchodilators, inhaled steroids, or local steroid.
* Has other active concomitant malignancy that warrants systemic, biologic, or hormonal therapy.
* Is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and/or for up to 180 days after the last dose of study treatment.
* Has a known history of Myelodysplastic syndrome (MDS) or Acute myeloid leukemia (AML).
* Has a known history of active tuberculosis.
* Has current active pneumonitis within 90 days of planned start of the study or a known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis requiring steroid treatment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
19/02/2025
Actual
Sample size
Target
Accrual to date
Final
666
Recruitment in Australia
Recruitment state(s)
NSW,TAS,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Blacktown
Recruitment hospital [2] 0 0
GSK Investigational Site - Hobart
Recruitment hospital [3] 0 0
GSK Investigational Site - Ballarat
Recruitment hospital [4] 0 0
GSK Investigational Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
7000 - Hobart
Recruitment postcode(s) [3] 0 0
3350 - Ballarat
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
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United States of America
State/province [4] 0 0
Florida
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United States of America
State/province [5] 0 0
Georgia
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Illinois
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Iowa
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Massachusetts
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New York
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North Carolina
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Virginia
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Argentina
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Buenos Aires
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Argentina
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Río Negro
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Argentina
State/province [18] 0 0
Santa Fe
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Argentina
State/province [19] 0 0
Ciudad Autónoma de Buenos Aires
Country [20] 0 0
Argentina
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Cordoba
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Belgium
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Brussels
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Belgium
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Edegem
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Leuven
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Roeselaere
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Espírito Santo
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Brazil
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Minas Gerais
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Paraná
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Brazil
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Rio Grande Do Sul
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Brazil
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Rio de Janeiro
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Brazil
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São Paulo
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Bulgaria
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Panagyurishte
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Bulgaria
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Pleven
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Plovdiv
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Ruse
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Chile
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Región Metro De Santiago
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Bogota
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Monteria
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Grenoble cedex 9
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Lille cedex
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Nantes cedex 1
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Rennes Cedex 9
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Strasbourg
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Toulon cedex
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Toulouse cedex 9
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Germany
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Schleswig-Holstein
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Germany
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Thueringen
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Germany
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Hamburg
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Larisa
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Maroussi
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N. Faliro
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Patra
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Hungary
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Törökbálint
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Sicilia
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Veneto
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Gyeonggi-do
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Korea, Republic of
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Seoul
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Korea, Republic of
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Suwon-Si
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Mexico
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Ciudad De Mexico
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Mexico
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Nuevo León
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Mexico
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Mexico City
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Mexico
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Puebla
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Amsterdam
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Den Bosch
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Netherlands
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Enschede
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Netherlands
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Maastricht
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Netherlands
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Utrecht
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Zwolle
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Drammen
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Norway
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Lørenskog
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Norway
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Oslo
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Lima
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Poland
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Bialystok
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Poland
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Lodz
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Poland
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Bucharest
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Romania
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Bucuresti
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Romania
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Cluj-Napoca
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Romania
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Craiova
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Romania
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Iasi
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Romania
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Satu Mare
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Romania
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Timisoara
Country [113] 0 0
Russian Federation
State/province [113] 0 0
Moscow
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Russian Federation
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Nizhniy Novgorod
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Russian Federation
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Omsk
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Russian Federation
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Saint-Petersburg
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Russian Federation
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St. Petersburg
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Spain
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Barcelona
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Spain
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Girona
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Spain
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La Coruña
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Spain
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Las Palmas De Gran Canaria
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Spain
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Madrid
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Spain
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Majadahonda (Madrid)
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Spain
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Málaga
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Spain
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Pamplona
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Spain
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Santander
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Spain
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Zaragoza
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Sweden
State/province [129] 0 0
Gävle
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Sweden
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Stockholm
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Sweden
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Uppsala
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Switzerland
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Lausanne
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Turkey
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Ankara
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Turkey
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Edirne
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Turkey
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Istanbul
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United Kingdom
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Middlesex
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United Kingdom
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Bournemouth
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United Kingdom
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Dundee
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United Kingdom
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Oxford
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United Kingdom
State/province [140] 0 0
Wrexham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled study of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in participants with advanced or metastatic non-small cell lung cancer (NSCLC) who have achieved stable disease (SD), partial response (PR), or complete response (CR) following completion of standard of care first-line platinum-based induction chemotherapy with pembrolizumab. The primary hypotheses are: participants with confirmed diagnosis of NSCLC could benefit from niraparib plus pembrolizumab versus placebo plus pembrolizumab with respect to Progression-free survival (PFS) and Overall survival (OS).
Trial website
https://clinicaltrials.gov/study/NCT04475939
Trial related presentations / publications
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. Erratum In: Cancer. 2023 Dec 15;129(24):3987. doi: 10.1002/cncr.35064.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04475939