Telaglenastat Hydrochloride and Osimertinib in Treating Patients With EGFR-Mutated Stage IV Non-small Cell Lung Cancer

Inclusion Criteria: * Histologically confirmed, stage IV NSCLC, with advanced or metastatic disease * Activating mutation present in the EGFR gene (L858R or exon 19 deletion, alone or in combination with other EGFR mutations) as per local assessment of a tissue biopsy/cytology specimen. The tissue biopsy must have been obtained since the time of disease progression on most recent targeted therapy. "Liquid" biopsies (i.e. blood based) biopsies cannot be used for eligibility determination * Patients must have had progressive disease on prior EGFR inhibitor therapy (gefitinib, erlotinib, afatinib, or osimertinib). There is no limit to lines of prior tyrosine kinase inhibitor (TKI) therapy. Prior osimertinib (AZD9291) therapy is permitted * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam * Age \> 18 years. NSCLC is exceedingly rare in patients \< 18 years of age. Because no dosing or adverse event (AE) data are currently available on the use of telaglenastat (CB-839) HCl in combination with osimertinib (AZD9291) in patients \< 18 years of age, children are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (K…