Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Aspiration

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Anti-Bacterial Agents

Antibodies

Antibodies, Monoclonal

Immune Checkpoint Inhibitors

Pembrolizumab

Vancomycin

Antibiotics, Antitubercular

Immunoglobulins

Aztreonam

Antineoplastic Agents, Immunological

Pembrolizumab + de-escalating doses of aztreonam and vancomycin

antibiotic with gram-negative bacteria coverage

aerosolized aztreonam

antibiotic with gram-positive bacteria coverage

aerosolized vancomycin

standard of care therapy/monoclonal antibody for patients with advanced NSCLC

pembrolizumab

Shannon G Swift, R.N.

Chen Zhao, M.D.

National Cancer Institute Referral Office

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.

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
* Received at least one previous line of standard frontline therapy that must include a PD-1/PD-L1-targeting ICI
* 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

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

Phase I Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-Small Cell Lung Cancer

.-- 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.

Safety will be evaluated by reported grades of toxicities, including DLTs at each dose levels.

Recommended phase 2 dose will be determined by reported grades of toxicities, including DLTs at each dose levels.

Feasibility will be reported as the fraction of participants who receive adequate doses of all drug agents without DLT at each dose level.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-small Cell Lung Cancer	NCT05777603	Advanced Non Sm...	aerosolized azt... aerosolized van... pembrolizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-small Cell Lung Cancer	NCT05777603	Advanced Non Sm...	aerosolized azt... aerosolized van... pembrolizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for aerosolized aztreonam