Clinical trial NCT04475939: Placebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants With Advanced/Metastatic Non-Small Cell Lung Cancer
Official 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Lung Cancer, Non-Small Cell
Keywords: Niraparib
Pembrolizumab
Maintenance therapy
Chemotherapy
Platinum-based
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-07-17
Enrollment: 666
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 (SoC 1L) 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).


Eligibility 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 SoC 1L 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 SoC 1L 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.

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.

Primary outcomes:
measure: Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 in complete and partial response (CR/PR) population
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: PFS assessed by BICR using RECIST v 1.1 in intent to treat (ITT) population
timeFrame: Up to approximately 3 years
measure: OS in CR/PR population
timeFrame: Up to approximately 3 years
measure: OS in overall population
timeFrame: Up to approximately 5 years
measure: Time to progression (TTP)
timeFrame: Up to approximately 3 years
measure: PFS by investigator assessment using RECIST v1.1
timeFrame: Up to approximately 3 years
measure: CNS PFS as assessed by BICR using RANO-BM
timeFrame: Up to approximately 3 years
measure: PFS as assessed by BICR using RECIST v1.1 by programmed cell death-ligand 1 (PD-L1) status
timeFrame: Up to approximately 3 years
measure: OS by PD-L1 status
timeFrame: Up to approximately 5 years
measure: Time to Deterioration (TTD) in Lung Symptoms
timeFrame: Up to approximately 3 years
measure: Change from Baseline in Health-related quality of life (HRQoL), functioning and symptoms by EORTC QLQ-C30-item Core module (EORTC QLQ-C30) (Scores on a scale)
timeFrame: 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)
measure: Change from Baseline in HRQoL functioning and symptoms by EORTC QLQ-LC13 (Scores on a scale)
timeFrame: 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)
measure: Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)
timeFrame: Up to approximately 3 years
measure: Plasma concentrations of niraparib
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Lone Tree
country: United States
facility: GSK Investigational Site
state: Colorado
city: Norwich
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Tallahassee
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Newnan
country: United States
facility: GSK Investigational Site
state: Georgia
city: Niles
country: United States
facility: GSK Investigational Site
state: Illinois
city: Iowa City
country: United States
facility: GSK Investigational Site
state: Iowa
city: Worcester
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Mineola
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: GSK Investigational Site
state: Texas
city: Waco
country: United States
facility: GSK Investigational Site
state: Texas
city: Fairfax
country: United States
facility: GSK Investigational Site
state: Virginia
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Cipoletti Rio Negro
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Cordoba
country: Argentina
facility: GSK Investigational Site
city: Florida
country: Argentina
facility: GSK Investigational Site
city: La Plata
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Blacktown
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Hobart
country: Australia
facility: GSK Investigational Site
state: Tasmania
city: Ballarat
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Heidelberg
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Roeselare
country: Belgium
facility: GSK Investigational Site
city: Belo Horizonte
country: Brazil
facility: GSK Investigational Site
city: Cachoeiro Do Itapemirim
country: Brazil
facility: GSK Investigational Site
city: Curitiba
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: UberlAndia
country: Brazil
facility: GSK Investigational Site
city: Panagyurishte
country: Bulgaria
facility: GSK Investigational Site
city: Pleven
country: Bulgaria
facility: GSK Investigational Site
city: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Ruse
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Temuco
country: Chile
facility: GSK Investigational Site
city: Bogota
country: Colombia
facility: GSK Investigational Site
city: Monteria
country: Colombia
facility: GSK Investigational Site
city: Brest cedex
country: France
facility: GSK Investigational Site
city: CrEteil cedex
country: France
facility: GSK Investigational Site
city: Grenoble Cedex 9
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Rennes
country: France
facility: GSK Investigational Site
city: Saint-Herblain
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Toulon cedex
country: France
facility: GSK Investigational Site
city: Toulouse cedex 9
country: France
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Bonn
country: Germany
facility: GSK Investigational Site
city: Essen
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
city: Gauting
country: Germany
facility: GSK Investigational Site
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
city: Halle
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hannover
country: Germany
facility: GSK Investigational Site
city: Heidelberg
country: Germany
facility: GSK Investigational Site
city: Hemer
country: Germany
facility: GSK Investigational Site
city: Jena
country: Germany
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
city: MUnchen
country: Germany
facility: GSK Investigational Site
city: Stuttgart
country: Germany
facility: GSK Investigational Site
city: Velbert
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Heraklion Crete
country: Greece
facility: GSK Investigational Site
city: Larissa
country: Greece
facility: GSK Investigational Site
city: Neo Faliro
country: Greece
facility: GSK Investigational Site
city: Patras
country: Greece
facility: GSK Investigational Site
city: Pylaia Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Rio Patras
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: GyOngyOs
country: Hungary
facility: GSK Investigational Site
city: TatabAnya
country: Hungary
facility: GSK Investigational Site
city: TOrOkbAlint
country: Hungary
facility: GSK Investigational Site
city: Cork
country: Ireland
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Avellino
country: Italy
facility: GSK Investigational Site
city: Aviano PN
country: Italy
facility: GSK Investigational Site
city: Bari
country: Italy
facility: GSK Investigational Site
city: Catania
country: Italy
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Monza
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Orbassano TO
country: Italy
facility: GSK Investigational Site
city: Pisa
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Verona
country: Italy
facility: GSK Investigational Site
city: Seongnam-si Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seongnam-si
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon Kyunggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Monterrey
country: Mexico
facility: GSK Investigational Site
city: Puebla Puebla
country: Mexico
facility: GSK Investigational Site
city: Amersfoort
country: Netherlands
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Den Bosch
country: Netherlands
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Maastricht
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Zwolle
country: Netherlands
facility: GSK Investigational Site
city: Drammen
country: Norway
facility: GSK Investigational Site
city: Lrenskog
country: Norway
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Cluj-Napoca
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Satu Mare
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Nizhniy Novgorod
country: Russian Federation
facility: GSK Investigational Site
city: Omsk
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: A CoruNa
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cordoba
country: Spain
facility: GSK Investigational Site
city: Gerona
country: Spain
facility: GSK Investigational Site
city: Las Palmas De Gran Canar
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: PamplonaNavarra
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Gavle
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Uppsala
country: Sweden
facility: GSK Investigational Site
city: Lausanne
country: Switzerland
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Edirne
country: Turkey
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
city: Bournemouth
country: United Kingdom
facility: GSK Investigational Site
city: Dundee
country: United Kingdom
facility: GSK Investigational Site
city: Middlesex
country: United Kingdom
facility: GSK Investigational Site
city: Oxford
country: United Kingdom
facility: GSK Investigational Site
city: Wrexham
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.