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

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