Advanced Non Small Cell Lung CancerPhase 1NCT05777603
Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-small Cell Lung Cancer
A Phase 1 study testing aerosolized aztreonam, aerosolized vancomycin and pembrolizumab in people with Advanced Non Small Cell Lung Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Advanced Non Small Cell Lung Cancer
- What is being tested?
- aerosolized aztreonam, aerosolized vancomycin and pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Apr 2024to 1 Jun 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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).
- Pulmonary function FEV1 (Forced Expiratory Volume in the first second) <25% will be excluded based on the requirement of receiving aerosolized aztreonam.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
National Cancer Institute Referral Office, 888-624-1937
About this study
Official title: Phase I Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-Small Cell Lung Cancer
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.
Read more
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.
Read the detailed 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 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
- Conditions
- Advanced Non Small Cell Lung Cancer
- Being tested
- aerosolized aztreonam, aerosolized vancomycin, pembrolizumab
- Keywords
- Immune Checkpoint Inhibitor, lung microbiota, anti-PD1 antibody, inhaled antibiotic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aerosolized aztreonamDrug
antibiotic with gram-negative bacteria coverage
aerosolized vancomycinDrug
antibiotic with gram-positive bacteria coverage
pembrolizumabDrug
standard of care therapy/monoclonal antibody for patients with advanced NSCLC
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Pembrolizumab + de-escalating doses of aztreonam and vancomycin Receives: Drug: aerosolized aztreonam; Drug: aerosolized vancomycin; Drug: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities (DLTs) - type and grade
Safety will be evaluated by reported grades of toxicities, including DLTs at each dose levels.
Measured: Start of therapy through 1 year after last study drug dose
Secondary outcomes (2)
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.
Measured: Start of therapy through 1 year after last study drug dose.
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.
Measured: Between start of therapy through 1 year after last study drug dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2023
- Study start18 Apr 2024
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Chen Zhao, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05777603
- Sponsor's protocol ID
- 10001516
- Other IDs
- 001516-C
- Status last verified
- 13 Oct 2026
- First submitted
- 18 Mar 2023
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: \-- All IPD recorded in the medical record will be shared with intramural investigators upon request. -- All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.