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.
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.
Patient s disease has progressed after FDA-approved frontline therapy for NSCLC.
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 individuals of childbearing potential at screening).
Single group
aerosolized aztreonam
Drugantibiotic with gram-negative bacteria coverage
aerosolized vancomycin
Drugantibiotic with gram-positive bacteria coverage
pembrolizumab
Drugstandard of care therapy/monoclonal antibody for patients with advanced NSCLC
Dose limiting toxicities (DLTs) - type and grade
Safety will be evaluated by reported grades of toxicities, including DLTs at each dose levels.
Dose limiting toxicities (DLTs) - type and grade
Recommended phase 2 dose will be determined by reported grades of toxicities, including DLTs at each dose levels.
Fraction of participants who received adequate doses of all agents at each dose level
Feasibility will be reported as the fraction of participants who receive adequate doses of all drug agents without DLT at each dose level.
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