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

NCT05777603 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001516001516-C
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Non Small Cell Lung Cancer

Keywords

Immune Checkpoint Inhibitor; lung microbiota; anti-PD1 antibody; inhaled antibiotic

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities (DLTs) - type and grade

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

  Start of therapy through 1 year after last study drug dose

Secondary Outcomes (2)

• Dose limiting toxicities (DLTs) - type and grade

  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

  Between start of therapy through 1 year after last study drug dose.

Study Arms (1)

Arm 1

EXPERIMENTAL

Pembrolizumab + de-escalating doses of aztreonam and vancomycin

Drug: aerosolized aztreonam; Drug: aerosolized vancomycin; Drug: pembrolizumab

Interventions

aerosolized vancomycin DRUG

antibiotic with gram-positive bacteria coverage

Arm 1

pembrolizumab DRUG

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

Arm 1

aerosolized aztreonam DRUG

antibiotic with gram-negative bacteria coverage

Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age \>=18 years.
• ECOG performance status \<=2.
• 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.
• Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Chen Zhao, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shannon G Swift, R.N.

CONTACT

(240) 858-3157; shannon.swift@nih.gov

Chen Zhao, M.D.

CONTACT

(301) 646-8331; chen.zhao@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2023
• First Posted: March 21, 2023
• Study Start: April 18, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-04-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: \-- Clinical data available during the study and indefinitely. -- Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: \-- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. -- Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)