non small cell lung cancer (NSCLC)
Conditions
Interventions
Niraparib/Placebo:
Niraparib/placebo will be administered orally once daily (2-3 tablets)
throughout each 21-day cycle until radiographic PD or another treatment
discontinuation criterion is met, or
Sponsors
GlaxoSmithKline
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Male or female, age 18 years and above. Diagnosis of NSCLC Advanced or metastatic NSCLC Completion of 4-6 cycles of platinum-based standard of care first-line induction chemotherapy with pembrolizumab Participants must have SD, PR, or CR of their NSCLC per Investigator*s assessment ECOG performance status 0-1. Life expectancy of at least 12 weeks. Adequate organ and bone marrow function Participants must submit FFPE tumor specimens Toxicity from induction therapy must have recovered to a level of organ and bone marrow function as defined by Inclusion Criteria #8 (see protocol) and no ongoing toxicity with grade 3 or higher. Able to swallow and retain orally administered study treatment. Contraception guidelines for females and males should be followed
Exclusion criteria
Exclusion criteria: Mixed small cell lung cancer or sarcomatoid variant NSCLC. Received prior PARP inhibitor(s) in prior lines of treatment. A systolic BP >140 mmHg or diastolic BP >90 mmHg. A clinically significant gastrointestinal abnormalities that may alter absorption. Leptomeningeal disease, carcinomatous meningitis, symptomatic BM, or radiographic signs of CNS hemorrhage. Received colony-stimulating factors within 4 weeks prior to the first dose of study treatment. Active or previously documented autoimmune or inflammatory disorder 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. Previously or currently participating in a treatment study with IP within 4 weeks of the first dose of standard of care first-line induction therapy. Received prior systemic cytotoxic chemotherapy, biological therapy or hormonal therapy for cancer, or received thoracic radiation therapy of >30 Gy within 6 months of the first dose of the start of standard of care first-line induction therapy. Received live vaccine within 30 days of planned start of study randomization. Known hypersensitivity to the components of niraparib, placebo, or pembrolizumab or their formulation excipients. Major surgery within 4 weeks of starting the first dose of study treatment or have not recovered from any effects of any major surgery. Active concomitant malignancy that warrants systemic, biologic or hormonal therapy. 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. Presence of hepatitis B or hepatitis C
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| OS is one of the dual primary endpoints for the study; it is defined as the time from randomization to the date of death due to any cause. Participants who are alive will be censored at the date of last contact. | — |
Secondary
| Measure | Time frame |
|---|---|
| The following key secondary efficacy endpoint will be evaluated: • PFS in NSQ population defined as per primary PFS endpoint • PFS in CR/PR population defined as per primary PFS endpoint • OS in NSQ population defined as per primary OS endpoint • OS in the CR/PR population • TTP in the CNS is defined as the time from the date of randomization until the earliest date of documented PD in the CNS. CNS progression is defined as progression in the CNS due to new CNS lesion or progression of baseline CNS lesion, as assessed by BICR per RANO-BM criteria. Secondary Efficacy Endpoints The following secondary efficacy endpoints will be evaluated: • PFS as assessed by the Investigator using RECIST v1.1 • PFS, per RECIST v1.1 based on BICR, and OS by PD-L1 status (PD-L1 TC =1%) • TTD, defined as the time from randomization to meaningful deterioration on a composite endpoint of dyspnea, chest pain, and cough, on the EORTC QLQ-LC13 • Change from baseline in the EORTC QLQ-C30 and EORTC QLQ-LC13 domains Safety Analysis (Secondary and Exploratory Endpoints) Safety will be evaluated based on the incidence of AEs, SAEs, and AESIs, the incidence of treatment discontinuations, dose interruptions, and dose reductions due to AEs, SAEs, or AESIs, changes in ECOG performance status, changes in clinical laboratory results (hematology, chemistry, thyroid function, and urinalysis), vital sign measurements, observations during physical examination, and use of concomitant medications | — |
Countries
Netherlands
Outcome results
None listed