NGS Screening Protocol to Detect Mutation of KEAP1 or NRF2/NFE2L2 Genes for the KEAPSAKE (CX-839-014) Trial

Study Overview
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Brief Summary
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This is a multicenter screening protocol designed to identify patients with NSCLC who have tumor mutations in the KEAP1 or NRF2/NFE2L2 genes in order to determine potential eligibility for a biomarker selected clinical trial (CX-839-014, otherwise known as the KEAPSAKE trial). Circulating tumor DNA (ctDNA) present in blood samples collected from eligible patients will be analyzed by next generation sequencing (NGS) for selected biomarkers. A commercial liquid biopsy NGS test will be provided to study participants free of charge.

Official Title
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Screening Protocol to Detect Mutation of KEAP1 or NRF2/NFE2L2 Genes in Patients With Stage IV, 1L Non-Small Cell Lung Cancer to Determine Eligibility for the KEAPSAKE Clinical Trial (NCT04265534)

Conditions
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Non-Small Cell Lung Cancer, Non-squamous Non-small-cell Lung Cancer, Non-Squamous Non-Small Cell Neoplasm of Lung, KEAP1 Gene Mutation, NRF2 Mutation, NFE2L2 Gene Mutation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with stage IV non-squamous non-small-cell lung cancer (NSCLC) who have not been previously treated with systemic therapy for metastatic disease, and meet all of the following: Signed and dated NGS Informed Consent Form (ICF) by the patient (or legally acceptable representative (LAR), if applicable). Biopsy-confirmed OR clinically suspected stage IV NSCLC not previously treated with systemic therapy for metastatic disease. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Age ≥ 18 years old on the day of signing informed consent. Estimated life expectancy > 3 months. At least one radiographically measurable lesion per RECIST v1.1 defined as a lesion that is ≥ 10 mm in longest diameter or lymph node that is ≥ 15 mm in short axis imaged by computed tomography (CT) scan or magnetic resonance imaging (MRI). Clinically eligible to receive standard-of-care combination therapy with pemetrexed + carboplatin + Pembrolizumab (PCP) for stage IV disease. Exclusion Criteria: Any contraindication to pemetrexed, carboplatin, and Pembrolizumab treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Biomarker Screening<br>Patients with stage IV nonsquamous NSCLC not previously treated with systemic therapy for metastatic disease and who meet all of study inclusion criteria and none of the exclusion criteria. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive KEAP1 or NRF2/NFE2L2 mutational status, assessed by NGS of blood ctDNA | The percentage of patients with nonsquamous NSCLC containing pathogenic NRF2/NFE2L2 and/or KEAP1 mutations | Up to 16 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alimta, KEAP1, NSCLC, NRF2, NFE2L2, LKB1, STK11, Next Generation Sequencing, NGS, Mutation, Gene, Pembrolizumab, Pemetrexed, Carboplatin, Placebo, Randomized, Chemotherapy, Immunotherapy, Targeted Therapy, Telaglenastat, Glutamine, Glutaminase, Glutathione, Front-line, First-line, Non-Squamous, Keytruda, Guardant360 LDT, Liquid Biopsy, ctDNA, Biomarker