Prognostic Value of Combined Approach Based on KEAP1/NFE2L2 Mutations and Pre-therapeutic FDG-PET/CT Radiomic Analysis in Advanced Non-small-cell Lung Cancer PDL1 ≥ 50% Treated With Pembrolizumab (PEMBROMIC)

NCT05996263 | Unknown

• 1 other identifier: 29BRC23.0142 - PEMBROMIC
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Lung Cancer Stage III; Lung Cancer Stage IV

Keywords

PDL1; PET/CT; Pembrolizumab; KEAP1/NFE2L2

Outcome Measures

Primary Outcomes (1)

• Progression-Free survival (PFS)

  PFS is defined as the time elapsed between initiation of treatment and tumor progression or death from any cause.

  through study completion, an average of 1 year

Secondary Outcomes (1)

• Overall Survival (OS)

  through study completion, an average of 1 year

Other Outcomes (1)

• Robustness of the prediction model

  through study completion, an average of 1 year

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients treated or being treated with immunotherapy alone with pembrolizumab in 1st-line metastatic NSCLC.

You may qualify if:

• Age ≥ 18 years
• Histologically or cytologically proven non-small-cell lung cancer (NSCLC)
• Stage IV NSCLC. Stage III NSCLC unresectable and not amenable to radiotherapy
• PD-L1 expression ≥ 50%.
• No previous systemic treatment for NSCLC.
• Patients treated for 1st-line metastatic disease with immunotherapy alone (pembrolizumab)
• No opposition expressed
• Patient affiliated to a social security scheme

You may not qualify if:

• PD-L1 expression \<50
• Neuroendocrine tumors
• Secondarily metastatic patients
• Previous treatments
• Opposition formulated
• Patient under legal protection (guardianship, curatorship, etc.)

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (1)

Chu Brest

Brest, 29609, France

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Vincent BOURBONNE, MD, PhD

  Radiation Oncology Department, Brest University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincent BOURBONNE, MD, PhD

CONTACT

+33298223398; vincent.bourbonne@chu-brest.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 18, 2023
• Study Start: August 1, 2023
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2024
• Last Updated: August 9, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available beginning three years and ending fifteen years following the final study report completion
• Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement

Locations

FR (1)