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No longer recruiting (closed or complete)Last updated: 17 March 2026

ZEAL-1L: This phase III trial is trying to improve maintenance therapy for patients with stage 3B or 4 non-small cell lung cancer who have remained stable or responded to first-line treatment. It will compare immunotherapy alone and in combination with an oral targeted therapy.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 or IV Non-Small Cell Lung Cancer

Trial purpose

Medical clipboardCancer treatment

Tumor type

Lung Cancers Lung cancer

Age

People18+

Trial acronym

ZEAL-1L

Clinical summary

Summary

Eligible patients will be randomised to receive 200mg of intravenous (IV) pembrolizumab over 30 minutes on Day 1 of each 21-day treatment cycle, in addition to a continuous, oral dose of Niraparib or Niraparib-placebo throughout the 21-day cycle starting on Cycle 1 (Day 1).

Conditions

This trial is treating people with non-small cell lung cancer (NSCLC)

Eligibility

Inclusion

  • 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

  • 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.

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • You are able to swallow medication by mouth.
  • You have had a certain type of treatment or surgical procedure.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

GlaxoSmithKline

Scientific 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 or IV Non-Small Cell Lung Cancer

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