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)

GlaxoSmithKline (GSK)

Status and phase: Active, not recruiting; Phase 3

Conditions: Lung Cancer, Non-Small Cell

Treatments: Biological: Pembrolizumab; Drug: Niraparib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04475939

213400

2023-508443-40 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 666 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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666 participants in 2 patient groups, including a placebo group

Participants receiving niraparib plus pembrolizumab

Experimental group

Description:

Eligible participants will receive niraparib along with pembrolizumab.

Treatment:

Biological: Pembrolizumab

Drug: Niraparib

Participants receiving placebo plus pembrolizumab

Placebo Comparator group

Description:

Eligible participants will receive matching placebo along with pembrolizumab.

Treatment:

Drug: Placebo

Biological: Pembrolizumab