Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-small Cell Lung Cancer

INCLUSION CRITERIA: Histologically or cytologically non-small cell lung cancer confirmed by outside pathology report or via the Laboratory of Pathology, NCI. Have measurable disease, per RECIST 1.1, that is not amenable to surgery. PD-L1 Tumor Proportion Score (TPS) >=1% detected at any time since diagnosis, based on a pathology report from an outside hospital or Laboratory of Pathology, NCI. PD- L1 expression testing must be conducted using one of the FDA approved diagnostic devices listed here: https://www.fda.gov/medical-devices/in-vitro-diagnostics/list- cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools. Received at least one previous line of standard frontline therapy that must include a PD-1/PD-L1-targeting ICI. Age >=18 years. ECOG performance status <=2. Must have adequate organ and marrow function as defined below: Leukocytes >=3,000/mcL absolute neutrophil count >=1,500/mcL platelets >=100,000/mcL total bilirubin<TAB>within normal institutional limits AST/ALT <=2.5 X institutional upper limit of normal creatinine clearance<TAB>>=60 mL/min/1.73 m^2 (calculated based on CKD-EPI formula or directly measured) for participants with creatinine levels above institutional normal. Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Participants with new or progressive brain metastases (active brain metastases) are eligible if immediate CNS specifictreatment is not required per standard of care and is unlikely to be required during the first cycle of therapy. Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within the 6 months before study treatment initiation are eligible for this trial. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Women of child-bearing potential (WOCBP) must agree to use effective contraception (e.g., hormonal intrauterine device [IUD], tubal ligation, partner has had prior vasectomy) beginning at study entry until 4 months after the completion of therapy. Note: abstinence, defined as no heterosexual sexual intercourse when this is in line with the preferred and usual lifestyle of the participant is also acceptable. Breastfeeding participants must be willing to discontinue breastfeeding for the duration of study treatment. Ability of participant to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: Participants who are receiving any other investigational agents. Participants with ongoing Epstein-Barr virus or cytomegalovirus infection History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab, aztreonam, vancomycin and albuterol. Pregnancy (confirmed with beta-HCG serum or urine pregnancy test performed in females of childbearing potential at screening). Pulmonary function FEV1 (Forced Expiratory Volume in the first second) <25% will be excluded based on the requirement of receiving aerosolized aztreonam. Participants with targetable EGFR, ALK, ROS1, BRAF V600E, NTRK1/2/3, METex14 skipping, RET, and HER2 genomic tumor aberrations. Genomic testing must be based on a pathology report from an outside hospital or Laboratory of Pathology, NCI and must be conducted using one of the FDA approved diagnostic devices listed here: https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or- approved-companion-diagnostic-devices-in-vitro-and-imaging-tools. Participants with KrasG12C mutation not previously treated with sotorasib or other approved KrasG12C small molecule inhibitor. History of severe immune-related adverse events (irAEs), defined as any grade neurological or cardiac irAEs, any grade 3 or 4 irAE (except fully controlled endocrine irAEs with appropriate hormone supplementation), and any grade pneumonitis. Uncontrolled intercurrent illness that would limit compliance with study requirements.