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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04475939
Ethics application status
Date submitted
14/07/2020
Date registered
17/07/2020
Date last updated
4/05/2021

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 - PFS is defined as the time from the date of randomization to the date of first radiographic progression as determined by BICR or death from any cause in the absence of progression, whichever occurs first.
Timepoint [1] 0 0
Up to approximately 3 years
Primary outcome [2] 0 0
Overall survival (OS) - OS is defined as the time from randomization to the date of death due to any cause.
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [1] 0 0
Time to progression (TTP) - TTP in the Central nervous system (CNS) is defined as the time from the date of randomization until the earliest date of documented PD in the CNS, based on BICR assessment using response assessment in neuro-oncology brain metastases (RANO-BM) criteria.
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [2] 0 0
PFS by investigator assessment - PFS is defined as the time from the date of randomization to the date of first radiographic progression as determined by the Investigator using RECIST v1.1 or death from any cause in the absence of progression, whichever occurs first.
Timepoint [2] 0 0
Up to approximately 3 years
Secondary outcome [3] 0 0
PFS by programmed cell death-ligand 1 (PD-L1) status - PFS is defined as the time from the date of randomization to the date of first radiographic progression as determined by BICR using RECIST v1.1 or death from any cause in the absence of progression, whichever occurs first. PFS will be assessed by PD-L1 status (PD-L1 tumor cells [TCs] less than [<]1% versus more than or equal to [>=]1%).
Timepoint [3] 0 0
Up to approximately 3 years
Secondary outcome [4] 0 0
OS by PD-L1 status - OS is defined as the time from randomization to the date of death due to any cause. OS will be assessed by PD-L1 status (PD-L1-TCs <1% versus >=1%).
Timepoint [4] 0 0
Up to approximately 5 years
Secondary outcome [5] 0 0
Time to Deterioration (TTD) in Lung Symptoms - TTD is defined as the time from randomization to meaningful deterioration as measured by (EORTC QLQ-LC13) questionnaire.
Timepoint [5] 0 0
Up to approximately 3 years
Secondary outcome [6] 0 0
Change from Baseline in Health-related quality of life (HRQoL) and symptoms by EORTC 30-item Core module (EORTC QLQ-C30) (Scores on a scale) - EORTC QLQ-C30 is a validated questionnaire to assess overall health-related quality of life in participants with cancer.
Timepoint [6] 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 [7] 0 0
Change from Baseline in HRQoL and symptoms by EORTC QLQ-LC13 (Scores on a scale) - The EORTC QLQ-LC13 is a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer participants.
Timepoint [7] 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 [8] 0 0
Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) - AEs, SAEs and AESIs will be collected.
Timepoint [8] 0 0
Up to approximately 3 years
Secondary outcome [9] 0 0
Plasma concentrations of niraparib - Blood samples will be collected to assess the plasma concentrations of niraparib.
Timepoint [9] 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).

- Has advanced (Stage IIIB not amenable to definitive chemoradiotherapy or Stage IIIC)
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 180 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
Gender
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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 postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
7000 - Hobart
Recruitment postcode(s) [3] 0 0
3350 - Ballarat
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
South Carolina
Country [5] 0 0
Argentina
State/province [5] 0 0
Buenos Aires
Country [6] 0 0
Argentina
State/province [6] 0 0
Santa Fe
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
Germany
State/province [8] 0 0
Baden-Wuerttemberg
Country [9] 0 0
Germany
State/province [9] 0 0
Hessen
Country [10] 0 0
Germany
State/province [10] 0 0
Nordrhein-Westfalen
Country [11] 0 0
Germany
State/province [11] 0 0
Sachsen-Anhalt
Country [12] 0 0
Germany
State/province [12] 0 0
Schleswig-Holstein
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Italy
State/province [14] 0 0
Campania
Country [15] 0 0
Italy
State/province [15] 0 0
Lombardia
Country [16] 0 0
Italy
State/province [16] 0 0
Piemonte
Country [17] 0 0
Italy
State/province [17] 0 0
Veneto
Country [18] 0 0
Netherlands
State/province [18] 0 0
Amersfoort
Country [19] 0 0
Netherlands
State/province [19] 0 0
Utrecht
Country [20] 0 0
Norway
State/province [20] 0 0
Lørenskog
Country [21] 0 0
Norway
State/province [21] 0 0
Oslo
Country [22] 0 0
Romania
State/province [22] 0 0
Bucuresti
Country [23] 0 0
Romania
State/province [23] 0 0
Cluj Napoca
Country [24] 0 0
Romania
State/province [24] 0 0
Cluj-Napoca
Country [25] 0 0
Romania
State/province [25] 0 0
Craiova
Country [26] 0 0
Romania
State/province [26] 0 0
Iasi
Country [27] 0 0
Romania
State/province [27] 0 0
Satu Mare
Country [28] 0 0
Romania
State/province [28] 0 0
Timisoara
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Moscow
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Omsk
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Saint-Petersburg
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Girona
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Majadahonda (Madrid)
Country [36] 0 0
Spain
State/province [36] 0 0
Málaga
Country [37] 0 0
Spain
State/province [37] 0 0
Pamplona
Country [38] 0 0
Spain
State/province [38] 0 0
Santander
Country [39] 0 0
Spain
State/province [39] 0 0
Zaragoza
Country [40] 0 0
Sweden
State/province [40] 0 0
Gävle
Country [41] 0 0
Sweden
State/province [41] 0 0
Stockholm
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Dundee

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/show/NCT04475939
Trial related presentations / publications
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
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

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