Description:
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).
Title
- Brief 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
- 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 IDs
- ORG STUDY ID:
213400
- NCT ID:
NCT04475939
Conditions
- Lung Cancer, Non-Small Cell
Interventions
| Drug | Synonyms | Arms |
|---|
| Niraparib | | Participants receiving niraparib plus pembrolizumab |
| Pembrolizumab | | Participants receiving niraparib plus pembrolizumab |
| Placebo | | Participants receiving placebo plus pembrolizumab |
Purpose
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 Arms
| Name | Type | Description | Interventions |
|---|
| Participants receiving niraparib plus pembrolizumab | Experimental | Eligible participants will receive niraparib along with pembrolizumab. | |
| Participants receiving placebo plus pembrolizumab | Placebo Comparator | Eligible participants will receive matching placebo along with pembrolizumab. | |
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).
- 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.
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 |
| Time Frame: | Up to approximately 3 years |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Time to progression (TTP) |
| Time Frame: | Up to approximately 3 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | PFS by investigator assessment |
| Time Frame: | Up to approximately 3 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | PFS by programmed cell death-ligand 1 (PD-L1) status |
| Time Frame: | Up to approximately 3 years |
| Safety Issue: | |
| Description: | 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%). |
| Measure: | OS by PD-L1 status |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | 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%). |
| Measure: | Time to Deterioration (TTD) in Lung Symptoms |
| Time Frame: | Up to approximately 3 years |
| Safety Issue: | |
| Description: | TTD is defined as the time from randomization to meaningful deterioration as measured by (EORTC QLQ-LC13) questionnaire. |
| Measure: | 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) |
| 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) |
| Safety Issue: | |
| Description: | EORTC QLQ-C30 is a validated questionnaire to assess overall health-related quality of life in participants with cancer. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | The EORTC QLQ-LC13 is a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer participants. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | AEs, SAEs and AESIs will be collected. |
| Measure: | Plasma concentrations of niraparib |
| Time Frame: | Up to approximately 3 years |
| Safety Issue: | |
| Description: | Blood samples will be collected to assess the plasma concentrations of niraparib. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | GlaxoSmithKline |
Trial Keywords
- Niraparib
- Pembrolizumab
- Maintenance therapy
- Chemotherapy
- Platinum-based
Last Updated
June 2, 2021
