Combining inhaled antibiotics with pembrolizumab for advanced lung cancer

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

This study is testing if using inhaled antibiotics along with a cancer drug can help people with advanced lung cancer feel better and improve their treatment results.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 18 Years to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: pembrolizumab
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05777603 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and feasibility of using two aerosolized antibiotics, aztreonam and vancomycin, in conjunction with the immune checkpoint inhibitor pembrolizumab for patients with advanced non-small cell lung cancer (NSCLC). Participants will undergo a series of treatments over six cycles, with assessments including physical exams, blood tests, lung function tests, and imaging scans. The goal is to determine if addressing lung microbiota dysbiosis can enhance the effectiveness of cancer treatment in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced NSCLC that has progressed after prior treatment and is not suitable for surgery.

Not a fit: Patients with NSCLC that is amenable to surgical intervention or those with a PD-L1 Tumor Proportion Score below 1% may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with advanced NSCLC by enhancing the efficacy of existing therapies.

How similar studies have performed: While the combination of antibiotics and immunotherapy is a novel approach, preclinical studies suggest potential benefits, though clinical evidence is limited.

Eligibility criteria

-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-companion-diagnostic-devices-in-vitro-and-imaging-tools.
4. Patient s disease has progressed after FDA-approved frontline therapy for NSCLC.
5. Age \>=18 years.
6. ECOG performance status \<=2.
7. Must have adequate organ and marrow function as defined below:

   * Leukocytes \>=3,000/mcL
   * absolute neutrophil count \>=1,500/mcL
   * platelets \>=100,000/mcL
   * total bilirubin\<TAB\>within normal institutional limits
   * AST/ALT \<=2.5 X institutional upper limit of normal
   * creatinine clearance \>=60 mL/min/1.73 m\^2 (calculated based on CKD-EPI formula or directly measured) for participants with creatinine levels above institutional normal.
8. Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
9. Participants with new or progressive brain metastases (active brain metastases) are eligible if immediate CNS specific treatment is not required per standard of care and is unlikely to be required during the first cycle of therapy.
10. Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within the 6 months before study treatment initiation are eligible for this trial.
11. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
12. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
13. Individuals of child-bearing potential (IOCBP) must agree to use effective contraception (e.g., hormonal intrauterine device \[IUD\], tubal ligation, partner has had prior vasectomy) beginning at study entry until 4 months after the completion of therapy. Note: abstinence, defined as no heterosexual sexual intercourse when this is in line with the preferred and usual lifestyle of the participant, is also acceptable.
14. Breastfeeding participants must be willing to discontinue breastfeeding for the duration of study treatment.
15. Ability of participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

1. Participants who are receiving any other investigational agents.
2. Participants with ongoing Epstein-Barr virus or cytomegalovirus infection
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab, aztreonam, vancomycin and albuterol.
4. Pregnancy (confirmed with beta-HCG serum or urine pregnancy test performed in individuals of childbearing potential at screening).
5. Pulmonary function FEV1 (Forced Expiratory Volume in the first second) \<25% will be excluded based on the requirement of receiving aerosolized aztreonam.
6. 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.
7. Uncontrolled intercurrent illness that would limit compliance with study requirements.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Chen Zhao, M.D. — National Cancer Institute (NCI)
• Study coordinator: Shannon G Swift, R.N.

Conditions Advanced Non Small Cell Lung Cancer; Immune Checkpoint Inhibitor; lung microbiota; anti-PD1 antibody; inhaled antibiotic