Niraparib Ph 3 – 1L Maintenance Non-Small Cell Lung Cancer with Niraparib in combination with pembrolizumab Simplified Title for public to understand

• Register: EUCTR
• Last refreshed on: 15 April 2024
• Main ID: EUCTR2020-002202-20-NL
• Date of registration: 08/10/2020
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd.
• Public title: Niraparib Ph 3 – 1L Maintenance Non-Small Cell Lung Cancer with Niraparib in combination with pembrolizumab Simplified Title for public to understand
• 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 forStage IIIB/IIIC or IV Non-Small Cell Lung Cancer (ZEAL 1L)
• Date of first enrolment: 18/12/2020
• Target sample size: 650
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002202-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Chile, China, Colombia, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Peru, Poland, Romania, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trials Help Desk
• Affiliation: GlaxoSmithKline Research & development Ltd

• Name: Clinical Trials Help Desk
• Affiliation: GlaxoSmithKline Research & development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Participants will be eligible for study entry if all of the following criteria are met:
1. Participants must be = 18 years of age. Note: Participants in Korea are eligible if they are ≥19 years of age at the time informed consent is obtained.
2. Participants must have 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.
3. Participants must have advanced (Stage IIIB not amenable to definitive chemoradiotherapy or stage IIIC) or metastatic (Stage IV) NSCLC as defined by the AJCC 8th Edition Staging Manual.
4. Participants must have completed at least 4 but no more than 6 cycles of standard of care first line platinum-based induction chemotherapy with pembrolizumab (according to standard of care defined by NCCN and/or ESMO Clinical Practice Guidelines for NSCLC).
Note: To support the transition from first-line (1L) induction to first-line maintenance therapy, a transition period that is 6 weeks, in duration, starting from the last dose of 1L induction therapy should occur (up to 7 weeks may be permitted with Sponsor approval). This transition period allows for recovery from chemotherapy-related hematological toxicity before initiating treatment with niraparib/placebo. During this transition period, pembrolizumab administration in the absence of chemotherapy should occur in the cycle immediately following the last cycle of 1L induction therapy (ie, 21 [±3] days after the last cycle of induction). If a transition period with administration of pembrolizumab only is not in accordance with standard prescribing directions and/or a pembrolizumab dose delay is needed that is greater than 3 weeks then the delay must be discussed with the Sponsor and reasons for the delay should be documented in the eCRF.
5. Participants must have SD, PR, or CR of their NSCLC per Investigator’s assessment after completion of 4 to 6 cycles of pembrolizumab plus platinum-based first-line induction chemotherapy with pembrolizumab.
Note: Baseline imaging may be done as part of standard of care first-line induction period so long as imaging is within 28 days of randomization. If baseline imaging falls outside of this 28-day window, then new imaging will be needed (CT [preferred] or MRI scan [if clinically indicated] of the chest and abdomen, and MRI [preferred; CT if MRI not possible] of the brain).
Note: For participants with only non-measurable/non-target disease at the onset of platinum-based induction therapy, a RECIST v1.1 response of non-complete response (CR)/non-progressive disease (PD) is consistent with SD as an overall response.
6. Participants must have an ECOG performance status of 0 or 1.
7. Participants must have a life expectancy of at least 12 weeks.
8. Participants must have adequate organ and bone marrow function defined as:
Absolute neutrophil count: =1,500/µL
Platelets: =100,000/µL
Hemoglobin: =9 g/dL or 5.6 mmol/L
CLCr: >30 mL/min as estimated by the Cockcroft Gault equation
Total bilirubin: =1.5 × ULN (except in participants with Gilbert’s syndrome.
Participants with Gilbert’s syndrome: isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct
bilirubin <35%)
AST and ALT: =2.5 × ULN (unless liver metastases are present, in which case
they must be =5 × ULN)
Note: CBC test should be obtained without
Exclusion criteria:
Participants will be excluded from study entry if any of the following criteria are met:
1. Participants have mixed small cell lung cancer or sarcomatoid variant NSCLC.
2. Participants have received prior PARP inhibitor(s) in prior lines of treatment.
3. Participants have systolic BP >140 mmHg and/or diastolic BP >90 mmHg.
4. Participants have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
5. Participants have leptomeningeal disease, carcinomatous meningitis, symptomatic BM, or radiographic signs of CNS hemorrhage.
Note: Participants with asymptomatic BM (ie, off corticosteroids and anticonvulsants for at least 7 days) are permitted.
6. Participants have received colony-stimulating factors (eg, granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 4 weeks prior to the first dose of study treatment.
7. Participants have active or previously documented autoimmune or inflammatory disorder, including:
a. Active infection
b. Known diagnosis of immunodeficiency (including known history of human immunodeficiency, HIV, or infection) or is receiving chronic systemic steroid therapy (eg, >30 days) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
c. Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
d. History of organ transplant
8. Participants are receiving chronic systemic steroids (prednisone >20 mg per day). Participants with asthma who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
9. Participants have previously or are currently participating in a treatment study of an investigational agent within 4 weeks of the first dose of standard of care first-line induction therapy preceding the study.
10. Participants have received prior systemic cytotoxic chemotherapy (IV or intraperitoneal), biological therapy (including checkpoint inhibitor), or hormonal therapy for cancer, or received thoracic radiation therapy of >30 Gy within 6 months of the first
dose of the start of first-line induction therapy.
11. Participants have received live vaccine within 30 days of planned start of study randomization.
12. Participants have known hypersensitivity to the components of niraparib, placebo, or pembrolizumab or their formulation excipients.
13. Participants have undergone major surgery within 4 weeks of starting the first dose of study treatment or have not recovered from any effects of any major surgery.
14. Participants have other active concomitant malignancy that warrants systemic, biologic, or hormonal therapy.
15. Participants have any clinically significant concomitant disease or condition (such as transfusion-dependent anemia or thrombocytopenia) that could interfere with, or for which the treatment might interfere with, the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable risk to the participants in this study.
16. Participants have any psychological, familial, sociological, or geographical condition potentially hampering

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-small Cell Lung Cancer
MedDRA version: 21.1 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Niraparib
Product Code: GSK3985771
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: NIRAPARIB
CAS Number: 1038915-60-4
Current Sponsor code: GSK3985771
Other descriptive name: niraparib tosylate monohydrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: KEYTRUDA
Product Name: Pembrolizumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Interim analysis (IA) is planned when approximately 404 OS events in the overall population and approximately 503 PFS events in the overall population are observed (44 months from FSFD) . This is the primary analysis for and the interim analysis for OS. The final OS analysis is planned when approximately 505 OS events are observed in the overall population (59 months from FSFD).

Main Objective: -To compare PFS as assessed by BICR using RECIST v1.1 of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in the overall population.

-To compare OS of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in the overall population

Secondary Objective: •To compare PFS as assessed by (BICR) using (RECIST v1.1) ofniraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in the non-squamous (NSQ) population
•To compare PFS as assessed by(BICR) using (RECIST v1.1) of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in best response to standard of care induction chemotherapy with (CR/PR) population
•To compare OS of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in the NSQ population
•To compare OS of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in the best response to standard of care induction chemotherapy with CR/PR population
-To evaluate and compare the TTP in the CNS as assessed by BICR using RANO-BM criteria
-To evaluate CNS PFS as assessed by BICR using RANO-BM.
-To evaluate PFS as assessed by the Investigator using RECIST v1.1
For more details please refer 15 page of Protocol v04

Primary end point(s): Compare progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors Version 1.1 of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy. Compare overall survival (OS) of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy. To evaluate and compare the time to progression (TTP) in the central nervous system (CNS) as assessed by BICR using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Ongoing throughout trial

Secondary end point(s): To compare PFS as assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in the NSQ population
To compare PFS as assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors version 1.1
(RECIST v1.1) of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in best response to standard of care induction chemotherapy with complete and partial response (CR/PR) population
To compare OS of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in the NSQ population
To compare OS of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in the best response to standard of care induction chemotherapy with CR/PR population
To evaluate PFS as assessed by the BICR Investigator using RECIST v1.1.
To evaluate CNS PFS as assessed by BICR using RANO-BM. Evaluate PFS as assessed by BICR using RECIST v1.1 and OS by programmed cell death ligand (PD-L1) status (PD-L1 tumor cells [TCs] <1% versus =1%).
To evaluate and compare time to deterioration in lung symptoms (TTD), defined as time from randomization to meaningful deterioration on a composite endpoint of dyspnea, chest pain, and cough, from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 13-item lung cancer-specific module (EORTC QLQ-LC13). To evaluate changes from baseline in health-related quality of life (HRQoL) and symptoms as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQ-C30) and the EORTC QLQ-LC13 total and domain scores. To evaluate safety and tolerability in participants treated with niraparib plus pembrolizumab compared to placebo plus pembrolizumab. To evaluate population pharmacokinetics (PK) of niraparib when given in combination with pembrolizumab.

Secondary ID(s)

2020-002202-20-GB

213400

Source(s) of Monetary Support

GlaxoSmithkline R&D

Ethics review

Status: Approved
Approval date: 18/12/2020
Contact: