Placebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants With Advanced/Metastatic Non-small Cell Lung Cancer

Lung Cancer, Non-Small Cell Clinical Trial

— ZEAL-1L  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04475939
• Other study ID #: 213400
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 26, 2020
• Est. completion date: February 19, 2025

Study information

• Verified date: February 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 666
• Est. completion date: February 19, 2025
• Est. primary completion date: December 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer, Non-Small Cell
• Lung Neoplasms

Intervention

Drug:
• Niraparib
Niraparib will be administered
• Pembrolizumab
Pembrolizumab will be administered
• Placebo
Matching placebo will be administered

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Cipoletti	Río Negro
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Florida	Buenos Aires
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Australia	GSK Investigational Site	Ballarat	Victoria
Australia	GSK Investigational Site	Blacktown	New South Wales
Australia	GSK Investigational Site	Heidelberg	Victoria
Australia	GSK Investigational Site	Hobart	Tasmania
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Edegem
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Roeselaere
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Cachoeiro Do Itapemirim	Espírito Santo
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	Uberlândia	Minas Gerais
Bulgaria	GSK Investigational Site	Panagyurishte
Bulgaria	GSK Investigational Site	Pleven
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Ruse
Bulgaria	GSK Investigational Site	Sofia
Chile	GSK Investigational Site	Providencia	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Temuco	Región De La Araucania
Colombia	GSK Investigational Site	Bogota
Colombia	GSK Investigational Site	Monteria
France	GSK Investigational Site	Brest cedex
France	GSK Investigational Site	Créteil cedex
France	GSK Investigational Site	Grenoble cedex 9
France	GSK Investigational Site	Lille cedex
France	GSK Investigational Site	Nantes cedex 1
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Rennes Cedex 9
France	GSK Investigational Site	Strasbourg
France	GSK Investigational Site	Toulon cedex
France	GSK Investigational Site	Toulouse cedex 9
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Gauting	Bayern
Germany	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein
Germany	GSK Investigational Site	Halle	Sachsen-Anhalt
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Hemer	Nordrhein-Westfalen
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Germany	GSK Investigational Site	Velbert	Nordrhein-Westfalen
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Heraklion,Crete
Greece	GSK Investigational Site	Larisa
Greece	GSK Investigational Site	Maroussi
Greece	GSK Investigational Site	N. Faliro
Greece	GSK Investigational Site	Patra
Greece	GSK Investigational Site	Rio/Patras
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Gyöngyös
Hungary	GSK Investigational Site	Tatabánya
Hungary	GSK Investigational Site	Törökbálint
Hungary	GSK Investigational Site	Zalaegerszeg
Ireland	GSK Investigational Site	Cork
Ireland	GSK Investigational Site	Dublin
Italy	GSK Investigational Site	Avellino	Campania
Italy	GSK Investigational Site	Aviano	Friuli-Venezia-Giulia
Italy	GSK Investigational Site	Bari	Puglia
Italy	GSK Investigational Site	Catania	Sicilia
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Legnago (VR)	Veneto
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Monza	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Orbassano (TO)	Piemonte
Italy	GSK Investigational Site	Pisa	Toscana
Italy	GSK Investigational Site	Roma	Lazio
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Seongnam-si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon-Si
Mexico	GSK Investigational Site	Mexico	Ciudad De Mexico
Mexico	GSK Investigational Site	Mexico City	Ciudad De Mexico
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Puebla
Netherlands	GSK Investigational Site	Amersfoort
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Den Bosch
Netherlands	GSK Investigational Site	Enschede
Netherlands	GSK Investigational Site	Maastricht
Netherlands	GSK Investigational Site	Utrecht
Netherlands	GSK Investigational Site	Zwolle
Norway	GSK Investigational Site	Drammen
Norway	GSK Investigational Site	Lørenskog
Norway	GSK Investigational Site	Oslo
Peru	GSK Investigational Site	Lima
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Olsztyn
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Satu Mare
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Nizhniy Novgorod
Russian Federation	GSK Investigational Site	Omsk
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Cordoba
Spain	GSK Investigational Site	Girona
Spain	GSK Investigational Site	La Coruña
Spain	GSK Investigational Site	Las Palmas De Gran Canaria
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Majadahonda (Madrid)
Spain	GSK Investigational Site	Málaga
Spain	GSK Investigational Site	Pamplona
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Zaragoza
Sweden	GSK Investigational Site	Gävle
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Uppsala
Switzerland	GSK Investigational Site	Lausanne
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Edirne
Turkey	GSK Investigational Site	Istanbul
United Kingdom	GSK Investigational Site	Bournemouth
United Kingdom	GSK Investigational Site	Dundee
United Kingdom	GSK Investigational Site	Northwood	Middlesex
United Kingdom	GSK Investigational Site	Oxford
United Kingdom	GSK Investigational Site	Wrexham
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Chattanooga	Tennessee
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Fairfax	Virginia
United States	GSK Investigational Site	Fleming Island	Florida
United States	GSK Investigational Site	Fullerton	California
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Lone Tree	Colorado
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Newnan	Georgia
United States	GSK Investigational Site	Niles	Illinois
United States	GSK Investigational Site	Norwich	Connecticut
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Sugar Land	Texas
United States	GSK Investigational Site	Waco	Texas
United States	GSK Investigational Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Chile,  Colombia,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Peru,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to approximately 3 years
Primary	Overall survival (OS) in overall population	OS is defined as the time from randomization to the date of death due to any cause.	Up to approximately 5 years
Secondary	PFS assessed by BICR using RECIST v 1.1 in non-squamous histology (NSQ) population	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	Up to approximately 3 years
Secondary	PFS assessed by BICR using RECIST v 1.1 in complete and partial response (CR/PR) population	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	Up to approximately 3 years
Secondary	OS in NSQ population	OS is defined as the time from randomization to the date of death due to any cause.	Up to approximately 5 years
Secondary	OS in CR/PR population	OS is defined as the time from randomization to the date of death due to any cause	Up to approximately 5 years
Secondary	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.	Up to approximately 3 years
Secondary	PFS by investigator assessment using RECIST v1.1	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.	Up to approximately 3 years
Secondary	CNS PFS as assessed by BICR using RANO-BM	PFS is defined as the time from the date of randomization to the date of first radiographic progression as determined by BICR using RANO-BM criteria.	Up to approximately 3 years
Secondary	PFS as assessed by BICR using RECIST v1.1 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% and not evaluable (NE) versus more than or equal to [>=]1%).	Up to approximately 3 years
Secondary	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% and NE versus >=1%).	Up to approximately 5 years
Secondary	Time to Deterioration (TTD) in Lung Symptoms	TTD is defined as the time from randomization to meaningful deterioration as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 13-item lung cancer-specific module (EORTC QLQ-LC13) questionnaire.	Up to approximately 3 years
Secondary	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)	EORTC QLQ-C30 is a validated questionnaire to assess overall health-related quality of life in participants with cancer.	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	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.	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	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.	Up to approximately 3 years
Secondary	Plasma concentrations of niraparib	Blood samples will be collected to assess the plasma concentrations of niraparib.	Up to approximately 3 years