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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04698681
Recruitment Status : Recruiting
First Posted : January 7, 2021
Last Update Posted : February 21, 2021
Information provided by (Responsible Party):
Calithera Biosciences, Inc

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.

Condition or disease Intervention/treatment Phase
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 Diagnostic Test: Liquid Biopsy NGS Test Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Stage IV, 1L Nonsquamous NSCLC patients to be screened for KEAP1 or NRF2(NFE2L2) gene mutations
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: 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)
Actual Study Start Date : January 19, 2021
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Biomarker Screening
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.
Diagnostic Test: Liquid Biopsy NGS Test
Ct-DNA from blood samples collected from eligible patients will be analyzed using NGS for the presence of mutations in either the NRF2/NFE2L2 or KEAP1 genes.

Primary Outcome Measures :
  1. Positive KEAP1 or NRF2/NFE2L2 mutational status, assessed by NGS of blood ctDNA [ Time Frame: Up to 16 months ]
    The percentage of patients with nonsquamous NSCLC containing pathogenic NRF2/NFE2L2 and/or KEAP1 mutations

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically documented nonsquamous NSCLC with Stage IV (M1a-c, AJCC 8th Edition) disease not previously treated with systemic therapy for metastatic NSCLC

    a. Patients who received adjuvant or neoadjuvant therapy (with or without immunotherapy) for localized NSCLC are eligible if all adjuvant/neoadjuvant therapy (including immunotherapy) was completed at least 6 months prior to the development of metastatic disease.

  • No known actionable mutation in EGFR, ALK, ROS1, BRAF, NTRK or other known actionable mutation for which there is approved therapy.
  • Measurable disease per RECIST 1.1.
  • Life expectancy of at least 3 months.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Age ≥ 18 years on the day of signing informed consent

Exclusion Criteria:

  • Squamous cell histology and mixed histology tumors with any small-cell component (other mixed histology and large cell neuroendocrine histology is allowed).
  • Known history of malignancy within the past three years except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or other neoplasm that, in the opinion of the principal investigator and with the agreement of the medical monitor, will not interfere with study-specific endpoints.
  • Had radiation therapy to the lung > 30 Gy within 6 months prior to randomization on the KEAPSAKE trial.
  • Has active autoimmune disease that has required systemic treatment in past 2 years.
  • Is currently receiving chronic systemic steroids greater than 10 mg equivalent of prednisone per day.
  • Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents).
  • Unable to swallow oral medications.
  • Known sensitivity to any component of the study treatment (pembrolizumab, carboplatin, pemetrexed, and/or telaglenastat) being tested in the KEAPSAKE trial or previous severe hypersensitivity to another monoclonal antibody
  • Unable or unwilling to take folic acid or vitamin B12 (intramuscular injection per label) supplementation.
  • Interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoid treatment
  • Unable or unwilling to discontinue proton pump inhibitors (PPI) at least 5 days before randomization on the KEAPSAKE trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04698681

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Contact: Clinical Administrator 650-870-1000
Contact: Clinical Admin

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Sponsors and Collaborators
Calithera Biosciences, Inc
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Study Director: Emil Kuriakose, MD Calithera Biosciences, Inc
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Responsible Party: Calithera Biosciences, Inc Identifier: NCT04698681    
Other Study ID Numbers: CX-839-016
First Posted: January 7, 2021    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Calithera Biosciences, Inc:
Next Generation Sequencing
Targeted Therapy
Guardant360 LDT
Liquid Biopsy
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms