This phase I/Ib trial studies the side effects and best dose of CB-839 HCl when given together with sapanisertib in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced). CB-839 HCl and sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Name: Sapanisertib
Name: Telaglenastat Hydrochloride
Description: Will be evaluated according to dose-limiting toxicities during cycle 1 graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Measure: Maximum tolerated dose/recommended phase II dose of MLN0128 (sapanisertib) and CB-839 HCl (telaglenastat) in combination (dose-escalation) Time: Up to 28 daysDescription: Response rate will be calculated for each cohort along with an exact 95% confidence interval.
Measure: Response rate (dose-expansion) Time: Up to 27 monthsDescription: Median PFS will be determined using the Kaplan-Meier method individual for each cohort and for all patients as well.
Measure: Median progression free survival (PFS) (dose-expansion) Time: Up to 27 monthsDescription: ORR will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Measure: Objective response rate (ORR) Time: Up to 27 monthsDescription: Will be evaluated by Kaplan-Meier estimates.
Measure: PFS Time: Up to 27 monthsDescription: DCR will be assessed by RECIST 1.1 criteria.
Measure: Disease control rate (DCR) Time: Up to 27 monthsDescription: Change in tumor uptake of radio-labelled glutamine on PET from baseline to cycle 1 day 8 will be quantified by the standardized uptake value maximum (SUVmax) (a standard PET parameter) in the largest measurable lesion. The before and after 18F-Gln PET values will be compared using log(after/before) as a measure of relative change.
Measure: Metabolic response (18Glutamine [GLN]-positron emission tomography [PET]/computed tomography [CT]; 18Fluorodeoxyglucose [FDG]-PET/CT) Time: Up to 27 monthsDescription: Genomic and metabolic signatures will be correlated with responses. Changes in glutamine, glutamate, aspartate, and asparagine will be measured, and responders will be compared to non-responders using a two-sample t-test or Wilcoxon test.
Measure: Genomic and metabolic signatures Time: Up to 27 monthsAllocation: N/A
Single Group Assignment
There is one SNP
Patients with autoimmune or other conditions where PD-(L)1 checkpoint inhibitors are contraindicated are eligible with progression on or after platinum-based chemotherapy or immunotherapy - Dose escalation: patients with NSCLC known to harbor EGFR, ALK, ROS1, BRAF V600E/K activating mutations must have also progressed on appropriate Food and Drug Administration (FDA)-approved targeted therapies to be eligible for dose escalation - Dose expansion: patients must have stage IV or recurrent/metastatic NSCLC harboring 1) NFE2L2 mutations (LSCC); 2) KEAP1 mutations (LSCC); KRAS/KEAP1 or KRAS/NFE2L2 co-mutations (non-squamous NSCLC); or 3) LSCC WT for NFE2L2 or KEAP1 who have progressed on or after platinum-based chemotherapy and/or PD (L)1 immune checkpoint inhibitors or immunotherapy. --- V600E ---