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

Background: * Dysbiosis of the lung microbiome is commonly seen in patients with advanced non-small cell lung cancer (NSCLC). It is associated with increased bacterial burden and decreased bacterial diversity in tumors * Preclinical studies using genetically engineered mouse (GEM) models show that dysbiosis of the lung microbiome promotes tumor growth in NSCLC Objective: \- To assess the safety of combined aerosolized antibiotics (aztreonam and vancomycin) with pembrolizumab IV, in participants with advanced NSCLC Eligibility: * Histological confirmation of NSCLC that is not amenable to surgery * Disease has progressed after FDA-approved frontline therapy for NSCLC * PD-L1Tumor Proportion Score (TPS) \>=1% detected at any time since diagnosis. * Measurable and progressive disease * Age \>=18 years * ECOG performance status \<=2 * Participants must have adequate organ and bone marrow function Design: * This is a phase I, open-label, single-arm study evaluating the safety and feasibility of combined aerosolized antibiotics (aztreonam and vancomycin) and pembrolizumab in advanced NSCLC * Participants will be given six cycles of treatments; each cycle is three weeks (21 days) * Participants receive pembrolizumab 200mg IV on Day 1 of each cycle * During cycles 1, 3 and 5, participants will self-administer aerosolized aztreonam 3 times a day and vancomycin twice a day from Day 2 through Day 21 * There are two dose levels of aerosolized antibiotics: participants start with Dose Level 1 (aztreonam 75mg three times a day and vancomycin 250mg twice a day) * If participants cannot tolerate Dose Level 1, treatment will be de-escalated to Dose Level * 1 (aztreonam 75mg once a day and vancomycin 250mg once a day) * Participants will be enrolled based on "3+3" scheme to test the primary endpoints of safety and feasibility * Up to 18 evaluable participants will be enrolled