Ignite Creation Date:
2024-05-06 @ 7:23 PM
Last Modification Date:
2024-10-26 @ 3:06 PM
Study NCT ID:
NCT05996263
Status:
RECRUITING
Last Update Posted:
2023-08-18
First Post:
2023-08-01
Brief Title:
Prognostic Value of Combined Approach Based on KEAP1NFE2L2 Mutations and Pre-therapeutic FDG-PETCT Radiomic Analysis in Advanced Non-small-cell Lung Cancer PDL1 50 Treated With Pembrolizumab PEMBROMIC
Sponsor:
University Hospital Brest
Organization:
University Hospital Brest
Study Overview
Official Title:
Prognostic Value of Combined Approach Based on KEAP1NFE2L2 Mutations and Pre-therapeutic FDG-PETCT Radiomic Analysis in Advanced Non-small-cell Lung Cancer PDL1 50 Treated With Pembrolizumab
Status:
RECRUITING
Status Verified Date:
2023-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PEMBROMIC
Brief Summary:
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 KEAP1NFE2L2 mutations predict radiation resistance in patients with localized NSCLC treated with radiotherapy but not surgery Some data also suggest a role for the KEAP1NFE2L2 axis in response to immunotherapy
Establishing a predictive model for the presence of the KEAP1NFE2L2 mutation would provide a tool for predicting survival progression-free and overall even before the patient starts immunotherapy
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 KEAP1NFE2L2 mutations predict radiation resistance in patients with localized NSCLC treated with radiotherapy but not surgery Some data also suggest a role for the KEAP1NFE2L2 axis in response to immunotherapy
Establishing a predictive model for the presence of the KEAP1NFE2L2 mutation would provide a tool for predicting survival progression-free and overall even before the patient starts immunotherapy
Detailed Description:
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 IIIBIV 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 35-15 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 KEAP1NFE2L2 mutations predict radiation resistance in patients with localized NSCLC treated with radiotherapy but not surgery Some data also suggest a role for the KEAP1NFE2L2 axis in response to immunotherapy
Establishing a predictive model for the presence of the KEAP1NFE2L2 mutation would provide a tool for predicting survival progression-free and overall even before the patient starts immunotherapy
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 IIIBIV 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 35-15 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 KEAP1NFE2L2 mutations predict radiation resistance in patients with localized NSCLC treated with radiotherapy but not surgery Some data also suggest a role for the KEAP1NFE2L2 axis in response to immunotherapy
Establishing a predictive model for the presence of the KEAP1NFE2L2 mutation would provide a tool for predicting survival progression-free and overall even before the patient starts immunotherapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None