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

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)

Status

Terminated

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT04698681

Enrollment

Registered

2021-01-07

Start date

2021-01-19

Completion date

2022-02-09

Last updated

2023-03-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

NSCLC, KEAP1, 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, Alimta, Guardant360 LDT, Liquid Biopsy, ctDNA, Biomarker

Brief summary

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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: 1. Signed and dated NGS Informed Consent Form (ICF) by the patient (or legally acceptable representative (LAR), if applicable). 2. Biopsy-confirmed OR clinically suspected stage IV NSCLC not previously treated with systemic therapy for metastatic disease. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. Age ≥ 18 years old on the day of signing informed consent. 5. Estimated life expectancy \> 3 months. 6. 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). 7. 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.

Design outcomes

Primary

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

Countries

United States

Outcome results