KEAPSAKE: A Study of Telaglenastat (CB-839) With Standard-of-Care Chemoimmunotherapy in 1L KEAP1/NRF2-Mutated, Nonsquamous NSCLC

Exclusion Criteria

• •1. Squamous cell histology and mixed histology tumors with any small-cell/neuroendocrine component (other mixed histology should be reviewed with the medical monitor for eligibility)
• •2. Any other concurrent malignancy requiring local or systemic therapy. Patients with other previously treated malignancy(ies) are allowed if the specific neoplasm, in the opinion of the principal investigator and with the agreement of the medical monitor, is not expected to interfere with study-specific endpoints
• •3. Radiation therapy to the lung \> 30 Gy within 6 months prior to randomization
• •4. Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis
• •5. Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
• •a. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• •6. Treatment with chronic systemic steroids greater than 10 mg equivalent of prednisone per day
• •7. Unstable/inadequate cardiac function, defined as the following:
• •1. Myocardial infarction or symptomatic ischemia within 6 months prior to randomization
• •2. Uncontrolled or clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with 1st degree atrioventricular \[AV\] block or asymptomatic left anterior fascicular block \[LAFB\]/right bundle branch block \[RBBB\] are eligible)
• •3. Congestive heart failure (New York Heart Association class III to IV)
• •8. Unable to swallow oral medications
• •9. Known sensitivity to any component of the study treatment (pembrolizumab, carboplatin, pemetrexed, and/or telaglenastat) or previous severe hypersensitivity to another monoclonal antibody (mAb)
• •10. Unable or unwilling to take folic acid or vitamin B12 supplementation (per pemetrexed label)
• •11. Unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) as specified in pemetrexed label
• •12. Interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoid treatment
• •13. Unable or unwilling to discontinue proton pump inhibitor (PPI) use ≥ 5 days prior to randomization
• •14. Patient known to be positive for Human Immunodeficiency Virus (HIV)
• •16. Any condition including social, psychiatric or medical (including uncontrolled significant concurrent illness) that in the opinion of the Investigator could interfere with treatment or protocol-related procedures
• •17. Regular use of illicit drugs or history (within past year) of substance abuse (including alcohol)
• •18. Patients who are pregnant or lactating
• •21. Symptomatic ascites or pleural effusion. Patients who are clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) are eligible
• •22. Refractory nausea and vomiting, uncontrolled diarrhea, malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes or other situation that may preclude adequate absorption or oral study drug
• •23. Infection requiring more than 5 days of parenteral antibiotics, antivirals, or antifungals within two weeks prior to randomization. Anti-infective therapy must be completed at least 7 days before randomization