Placebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants With Advanced/Metastatic Non-small Cell Lung Cancer (ZEAL-1L)
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| ClinicalTrials.gov Identifier: NCT04475939 |
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Recruitment Status :
Active, not recruiting
First Posted : July 17, 2020
Last Update Posted : February 5, 2024
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Sponsor:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lung Cancer, Non-Small Cell | Drug: Niraparib Drug: Pembrolizumab Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 666 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Multicenter, randomized, double-blind, placebo-controlled study. |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Masking Description: | The participant, Investigator, study staff, and the Sponsor study team will be blinded. |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | October 26, 2020 |
| Estimated Primary Completion Date : | December 20, 2024 |
| Estimated Study Completion Date : | February 19, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
MedlinePlus related topics:
Lung Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Participants receiving niraparib plus pembrolizumab
Eligible participants will receive niraparib along with pembrolizumab.
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Drug: Niraparib
Niraparib will be administered Drug: Pembrolizumab Pembrolizumab will be administered |
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Placebo Comparator: Participants receiving placebo plus pembrolizumab
Eligible participants will receive matching placebo along with pembrolizumab.
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Drug: Pembrolizumab
Pembrolizumab will be administered Drug: Placebo Matching placebo will be administered |
Primary Outcome Measures :
- 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 [ Time Frame: Up to approximately 3 years ]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.
- Overall survival (OS) in overall population [ Time Frame: Up to approximately 5 years ]OS is defined as the time from randomization to the date of death due to any cause.
Secondary Outcome Measures :
- PFS assessed by BICR using RECIST v 1.1 in non-squamous histology (NSQ) population [ Time Frame: Up to approximately 3 years ]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
- PFS assessed by BICR using RECIST v 1.1 in complete and partial response (CR/PR) population [ Time Frame: Up to approximately 3 years ]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
- OS in NSQ population [ Time Frame: Up to approximately 5 years ]OS is defined as the time from randomization to the date of death due to any cause.
- OS in CR/PR population [ Time Frame: Up to approximately 5 years ]OS is defined as the time from randomization to the date of death due to any cause
- Time to progression (TTP) [ Time Frame: Up to approximately 3 years ]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.
- PFS by investigator assessment using RECIST v1.1 [ Time Frame: Up to approximately 3 years ]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.
- CNS PFS as assessed by BICR using RANO-BM [ Time Frame: Up to approximately 3 years ]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.
- PFS as assessed by BICR using RECIST v1.1 by programmed cell death-ligand 1 (PD-L1) status [ Time Frame: Up to approximately 3 years ]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%).
- OS by PD-L1 status [ Time Frame: Up to approximately 5 years ]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%).
- Time to Deterioration (TTD) in Lung Symptoms [ Time Frame: Up to approximately 3 years ]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.
- 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) [ Time Frame: 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) ]EORTC QLQ-C30 is a validated questionnaire to assess overall health-related quality of life in participants with cancer.
- Change from Baseline in HRQoL and symptoms by EORTC QLQ-LC13 (Scores on a scale) [ Time Frame: 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) ]The EORTC QLQ-LC13 is a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer participants.
- Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) [ Time Frame: Up to approximately 3 years ]AEs, SAEs and AESIs will be collected.
- Plasma concentrations of niraparib [ Time Frame: Up to approximately 3 years ]Blood samples will be collected to assess the plasma concentrations of niraparib.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04475939
Locations
Show 191 study locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
| Study Director: | GSK Clinical Trials | GlaxoSmithKline |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | GlaxoSmithKline |
| ClinicalTrials.gov Identifier: | NCT04475939 |
| Other Study ID Numbers: |
213400 |
| First Posted: | July 17, 2020 Key Record Dates |
| Last Update Posted: | February 5, 2024 |
| Last Verified: | February 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/ |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) |
| Time Frame: | Anonymized IPD will be 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. |
| URL: | https://www.gsk.com/en-gb/innovation/trials/data-transparency/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by GlaxoSmithKline:
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Niraparib Pembrolizumab Maintenance therapy Chemotherapy Platinum-based |
Additional relevant MeSH terms:
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic |
Bronchial Neoplasms Pembrolizumab Niraparib Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors |