An observational study in Lung Cancer Stage III and Lung Cancer Stage IV, sponsored by University Hospital, Brest. Recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-09.
Sponsored by University Hospital, Brest · Observational
Pembrolizumab has been approved for first-line locally advanced or metastatic NSCLC with a tumor proportion score (TPS) ≥50% for PDL1, based on the results of KEYNOTE-024.
However, even with a positive PDL1 status, only a fraction of patients respond to immunotherapy. In the KEYNOTE-024 study evaluating pembrolizumab versus chemotherapy in first-line advanced NSCLC with PDL1 TPS ≥50%, the response rate in the pembrolizumab arm alone was 45%. NFE2L2 is a transcription factor that directs the expression of free radical defense genes that may interfere with radiation-induced DNA damage. KEAP1 is an adaptor protein that targets NFE2L2 for ubiquitination and proteasomal destruction as part of normal homeostasis. These new biomarkers are of clinical interest, as KEAP1/NFE2L2 mutations predict radiation resistance in patients with localized NSCLC treated with radiotherapy but not surgery. Some data also suggest a role for the KEAP1/NFE2L2 axis in response to immunotherapy.
Establishing a predictive model for the presence of the KEAP1/NFE2L2 mutation would provide a tool for predicting survival (progression-free and overall), even before the patient starts immunotherapy.
Pembrolizumab has been approved for first-line locally advanced or metastatic NSCLC with a tumor proportion score (TPS) ≥50% for PDL1, based on the results of KEYNOTE-024.
However, even with a positive PDL1 status, only a fraction of patients respond to immunotherapy. In the KEYNOTE-024 study evaluating pembrolizumab versus chemotherapy in first-line advanced NSCLC with PDL1 TPS ≥50%, the response rate in the pembrolizumab arm alone was 45%. This result led to the approval of pembrolizumab for first-line advanced NSCLC with PDL1 TPS ≥ 50%, which nevertheless represents only 22% of patients with stage IIIB/IV NSCLC.
Early identification of biomarkers for patients unlikely to benefit from first-line pembrolizumab is therefore a crucial step in selecting suitable candidates.
Furthermore, in cancer, genomic alterations in NFE2L2, KEAP1 and CUL3 result in constitutive activation of NRF2-dependent gene transcription, which promotes cellular resistance to oxidative stress, xenobiotic efflux, proliferation and metabolic reprogramming. Somatic mutations in NFE2L2 and KEAP1 are found in 3.5-15% and 12-17% of NSCLC patients respectively. NFE2L2 is a transcription factor that directs the expression of free radical defense genes that may interfere with radiation-induced DNA damage. KEAP1 is an adaptor protein that targets NFE2L2 for ubiquitination and proteasomal destruction as part of normal homeostasis. These new biomarkers are of clinical interest, as KEAP1/NFE2L2 mutations predict radiation resistance in patients with localized NSCLC treated with radiotherapy but not surgery. Some data also suggest a role for the KEAP1/NFE2L2 axis in response to immunotherapy.
Establishing a predictive model for the presence of the KEAP1/NFE2L2 mutation would provide a tool for predicting survival (progression-free and overall), even before the patient starts immunotherapy.
7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.
This study's planned enrollment of 75 is below the median of 189 across 1,514 observational studies indexed under Lung Neoplasms.
Browse Lung Neoplasms studies →University Hospital, Brest is the lead sponsor of 594 studies on the registry; 135 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients treated or being treated with immunotherapy alone with pembrolizumab in 1st-line metastatic NSCLC.
Exclusion Criteria:
Progression-Free survival (PFS)
PFS is defined as the time elapsed between initiation of treatment and tumor progression or death from any cause.
Time frame: through study completion, an average of 1 year
Overall Survival (OS)
OS is defined as the time elapsed between initiation of treatment and death, whatever the cause.
Time frame: through study completion, an average of 1 year
Robustness of the prediction model
Robustness will be assessed by comparing predictions obtained from 2 different blind reviewers
Time frame: through study completion, an average of 1 year
Plan to share: Yes — All collected data that underlie results in a publication
Supporting information: Study protocol
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University Hospital, Brest