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

Plain English Summary

Study of Aerosolized Antibiotics and Pembrolizumab in Advanced Non-small Cell Lung Cancer is a Phase 1 clinical trial sponsored by National Cancer Institute (NCI) studying Advanced Non Small Cell Lung Cancer. This trial is testing if inhaled antibiotics, given alongside a standard cancer drug, can help treat advanced non-small cell lung cancer. It is for adults with non-small cell lung cancer that has returned or grown after previous treatment and cannot be removed by surgery. Participants will receive the cancer drug intravenously and inhale antibiotics as a mist at home, with regular check-ups and tests. Alternative treatments include other chemotherapy, immunotherapy, or targeted therapies depending on the specific cancer characteristics. The trial aims to enroll 23 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with non-small cell lung cancer that has spread and cannot be surgically treated. Patients must have had their cancer progress after standard treatments and have a specific marker (PD-L1) in their tumor. Individuals with certain pre-existing health conditions, such as uncontrolled infections or severe immune-related side effects from prior treatments, may not be eligible. Good general health, including adequate blood counts and organ function, is required. This trial is studying Advanced Non Small Cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how safe the combination treatment is by looking at any serious side effects that might limit the dose of the study drugs. The specific primary outcome measures are: Dose limiting toxicities (DLTs) - type and grade (Start of therapy through 1 year after last study drug dose). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses the unmet need in treating advanced non-small cell lung cancer by exploring how targeting lung bacteria with antibiotics might improve the effectiveness of immunotherapy. This research targets Advanced Non Small Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This early-phase trial, sponsored by the NCI, investigates a novel combination therapy for a significant cancer market, with potential to improve immunotherapy response rates. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for your specific type of lung cancer and if the potential benefits outweigh the risks. Be prepared for regular clinic visits for the cancer drug and to manage inhaling antibiotics at home, which requires consistent use. Understand that this is an early-phase study, meaning its main goal is to assess safety and find the right dose, not necessarily to prove effectiveness yet. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 23 participants

Interventions

• DRUG: aerosolized aztreonam — antibiotic with gram-negative bacteria coverage
• DRUG: aerosolized vancomycin — antibiotic with gram-positive bacteria coverage
• DRUG: pembrolizumab — standard of care therapy/monoclonal antibody for patients with advanced NSCLC

Primary Outcomes

• Dose limiting toxicities (DLTs) - type and grade (Start of therapy through 1 year after last study drug dose)

Secondary Outcomes

• 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.)

Full 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.

Trial Locations

• National Institutes of Health Clinical Center, Bethesda, Maryland, United States

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• Lung Cancer
• Cancer
• Malignant Neoplasms
• Respiratory Tract Neoplasms
• Neoplasms
• Immunotherapy
• Antibiotic Therapy
• Bacterial Infections
• Oncology

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