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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 666
- 试验地点
- 188
- 主要终点
- Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) - Complete and Partial Response (CR/PR) Population
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The participant Investigator study staff and the Sponsor study team will be blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Participants receiving placebo plus pembrolizumab
Eligible participants will receive matching placebo along with pembrolizumab.
干预措施: Pembrolizumab (Biological)
Participants receiving niraparib plus pembrolizumab
Eligible participants will receive niraparib along with pembrolizumab.
干预措施: Niraparib (Drug)
Participants receiving niraparib plus pembrolizumab
Eligible participants will receive niraparib along with pembrolizumab.
干预措施: Pembrolizumab (Biological)
Participants receiving placebo plus pembrolizumab
Eligible participants will receive matching placebo along with pembrolizumab.
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) - Complete and Partial Response (CR/PR) Population
时间窗: Up to 52 months
PFS is defined as the time from the date of randomization to the date of first objectively documented disease progression (PD) as determined by blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or death from any cause in the absence of progression, whichever occurs first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
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
时间窗: Up to approximately 3 years
PFS in CR/PR population 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.
次要结局
- Progression-free Survival (PFS) Assessed by BICR - Intent-to-Treat (ITT) Population(Up to 52 months)
- Overall Survival (OS) - CR/PR Population(Up to 52 months)
- Overall Survival (OS) - ITT Population(Up to 52 months)
- Time to Progression (TTP) in the Central Nervous System (CNS) Assessed by BICR Using RANO-BM Criteria(At Month 6, 12, 18, 24, 30, 36, 42 and 48)
- Progression-free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1(Up to 52 months)
- CNS-PFS as Assessed by BICR Using RANO-BM Criteria(At Month 6, 12, 18, 24, 30, 36, 42 and 48)
- Progression-free Survival (PFS) by Programmed Cell Death-ligand 1 (PD-L1) Status(Up to 52 months)
- Overall Survival by Programmed Cell Death-ligand 1 (PD-L1) Status(Up to 52 months)
- Number of Participants With Minimally Clinically Important Difference (MCID) Status in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30)(Baseline (Predose); Day (D) 1 of Cycle (C)2, C3, C4, C5-C67 (odd cycles only); End of Treatment (EoT, up to approx 49 months); Safety follow-up (SFU) 1 & 2 (up to approx 50 & 52 months))
- Changes From Baseline (CFB) in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 13-item Lung Cancer-specific Module (EORTC QLQ-LC13)(Baseline (Predose); Day (D) 1 of Cycle (C)2, C3, C4, C5-C67 (odd cycles only); EoT (up to approx 49 months); Safety follow-up (SFU) 1 & 2 (up to approx 50 & 52 months))
- Time to Deterioration (TTD) in EORTC Cancer Quality of Life Questionnaire LC13 (EORTC QLQ-LC13)(Up to 52 months)
- Number of Participants With Treatment Emergent (TE) Adverse Events (AEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)(Up to 52 months)
- Plasma Concentrations of Niraparib(Cycle 1 Day 1 (pre-dose, 3 h), Cycle 1 Day 15 (pre-dose, 3 h), Cycle 2 Day 1 (pre-dose, 3 h), Cycle 4 Day 1 (pre-dose), Cycle 7 Day 1 (pre-dose), and End of Treatment (pre-dose); up to approximately 49 months)
- PFS assessed by BICR using RECIST v 1.1 in intent to treat (ITT) population(Up to approximately 3 years)
- OS in CR/PR population(Up to approximately 3 years)
- OS in overall population(Up to approximately 5 years)
- Time to progression (TTP)(Up to approximately 3 years)
- PFS by investigator assessment using RECIST v1.1(Up to approximately 3 years)
- CNS PFS as assessed by BICR using RANO-BM(Up to approximately 3 years)
- PFS as assessed by BICR using RECIST v1.1 by programmed cell death-ligand 1 (PD-L1) status(Up to approximately 3 years)
- OS by PD-L1 status(Up to approximately 5 years)
- Time to Deterioration (TTD) in Lung Symptoms(Up to approximately 3 years)
- 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)(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))
- Change from Baseline in HRQoL functioning and symptoms by EORTC QLQ-LC13 (Scores on a scale)(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))
- Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)(Up to approximately 3 years)
- Plasma concentrations of niraparib(Up to approximately 3 years)