Phase I Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-Small Cell Lung Cancer
National Cancer Institute (NCI)
Summary
Background: Non-small cell lung cancer (NSCLC) can be hard to treat and is often fatal. People with NSCLC commonly have changes in the bacteria that populate their lungs. These bacterial changes may aid tumor growth. Researchers want to find out if treating the bacteria, too, can help cancer treatment work better. Objective: To test 2 inhaled antibiotics (aztreonam and vancomycin), combined with a standard cancer treatment, in people with NSCLC. Eligibility: People aged 18 years and older with NSCLC that has returned or progressed after treatment and cannot be treated with surgery. Design: Participants will be screened. They will have a physical exam with blood tests. They may blow into a machine to test how well their lungs work. They will have imaging scans. They may need to have a small piece of tissue cut from their tumor (biopsy). Participants will be treated in six 21-day cycles. They will visit the clinic to receive a drug for cancer treatment on the first day of each cycle. This drug will be administered through a tube attached to a needle inserted into a vein in the arm. The 2 antibiotic drugs will be in the form of a fine mist that can be inhaled. Participants use a device to take these drugs at home. They will inhale aztreonam up to 3 times a day and vancomycin 1 or 2 times a day. They will take these drugs during only 3 of the treatment cycles. Biopsies and other tests will be repeated halfway through and after the study treatment. Follow-up visits will continue for 1 year after study treatment.
Description
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 s…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
-INCLUSION CRITERIA: 1. Histologically or cytologically non-small cell lung cancer confirmed by outside pathology report or via the Laboratory of Pathology, NCI. 2. Have measurable disease, per RECIST 1.1, that is not amenable to surgery. 3. 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-com…
Interventions
- Drugaerosolized aztreonam
antibiotic with gram-negative bacteria coverage
- Drugaerosolized vancomycin
antibiotic with gram-positive bacteria coverage
- Drugpembrolizumab
standard of care therapy/monoclonal antibody for patients with advanced NSCLC
Location
- National Institutes of Health Clinical CenterBethesda, Maryland