Aerosolized Antibiotics + Pembrolizumab for Lung Cancer

Overseen By Chen Zhao, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Severe irAEs, Genomic aberrations, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 18 weeks

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if inhaled antibiotics combined with a standard cancer drug, Pembrolizumab, can enhance treatment for non-small cell lung cancer (NSCLC). NSCLC is difficult to treat and often recurs after initial therapy. Researchers believe that altering lung bacteria with antibiotics may help combat the cancer more effectively. The trial is suitable for individuals whose NSCLC has returned or advanced after previous treatment and cannot be surgically removed. Participants will inhale two antibiotics at home while receiving a standard cancer drug in a clinic over several treatment cycles. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pembrolizumab, a cancer treatment, is usually well-tolerated by people with lung cancer. Some studies suggest it helps people live longer when combined with chemotherapy. However, like all treatments, it can cause side effects, such as tiredness or nausea.

Regarding the antibiotics aztreonam and vancomycin, they are generally safe for treating infections. When inhaled, they might cause mild side effects like coughing or a sore throat. This study is in its early stages, so researchers are closely monitoring safety. The trial primarily aims to determine if using these antibiotics with pembrolizumab is safe for people with non-small cell lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of aerosolized antibiotics and pembrolizumab for lung cancer because it introduces a novel way to enhance immune response against tumors. Unlike traditional chemotherapy, which can be harsh on the body, this treatment uses pembrolizumab, an immunotherapy drug, to help the immune system recognize and attack cancer cells. Additionally, the use of aerosolized antibiotics like aztreonam and vancomycin aims to target infections in the lungs more directly, potentially reducing inflammation and improving the overall effectiveness of the cancer treatment. This dual approach not only targets the cancer but also tackles lung infections, which is quite different from the standard treatments available today.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Studies have shown that pembrolizumab, a common cancer treatment, can help patients with non-small cell lung cancer (NSCLC) live longer. Research indicates that patients receiving pembrolizumab have better survival rates than those undergoing traditional chemotherapy. In this trial, participants will receive a combination of pembrolizumab with de-escalating doses of aztreonam and vancomycin, two inhaled antibiotics. These antibiotics aim to target lung bacteria that might aid tumor growth. Although direct evidence of these antibiotics working against cancer is limited, they show promise in altering lung bacteria. By combining these antibiotics with pembrolizumab, the treatment aims to be more effective against NSCLC. ^{1 3 4 6 7}

Who Is on the Research Team?

Chen Zhao, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with advanced non-small cell lung cancer (NSCLC) that's worsened after treatment and can't be surgically removed. They must have had prior therapy targeting PD-1/PD-L1, measurable disease, proper organ function, no severe allergies to trial drugs or similar compounds, and agree to use contraception if applicable.

Inclusion Criteria

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

I am breastfeeding but willing to stop during the study.

I am HIV-positive, on effective treatment, and my viral load has been undetectable for the last 6 months.

Exclusion Criteria

Participants who are receiving any other investigational agents

My lung function is better than 25% of the expected value.

I have had severe side effects from immune therapy affecting my nerves, heart, lungs, or were very serious.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pembrolizumab IV on Day 1 of each 21-day cycle, and self-administer aerosolized antibiotics during cycles 1, 3, and 5

18 weeks

6 visits (in-person) for pembrolizumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Aztreonam
• Pembrolizumab
• Vancomycin

Trial Overview The study tests two inhaled antibiotics (aztreonam and vancomycin), combined with pembrolizumab (a standard cancer drug), for NSCLC. Participants will undergo six cycles of treatment including clinic visits for pembrolizumab infusions and at-home inhalation of the antibiotics during three cycles.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 3 Interventions

Pembrolizumab + de-escalating doses of aztreonam and vancomycin

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05777603

NCT05777603 | Study of Aerosolized Antibiotics and ... Objective: To test 2 inhaled antibiotics (aztreonam and vancomycin), combined with a standard cancer treatment, in people with NSCLC. Eligibility: People aged ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10082298/

Five-Year Outcomes With Pembrolizumab Versus ... KEYNOTE-042 is a randomized phase III study that showed significantly longer overall survival (OS) with pembrolizumab monotherapy versus platinum-based ...

3. withpower.com withpower.com/trial/phase-1-lung-neoplasms-2-2023-ed129

Aerosolized Antibiotics + Pembrolizumab for Lung Cancer What data supports the effectiveness of the drug pembrolizumab for lung cancer? Pembrolizumab has been shown to improve survival in patients with non-small cell ...

4. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40157574/

the phase III 3475A-D77 trial Conclusions: Overall exposure and trough concentrations of pembrolizumab s.c. 790 mg q6w were noninferior to those of pembrolizumab i.v. 400 mg q6w given with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9942927/

Effectiveness and safety of pembrolizumab for patients with ... In addition, the 5-year survival rate for lung cancer ranges from approximately 10%~20% in most countries (4). Lung cancer includes small cell ...

7. merckclinicaltrials.com merckclinicaltrials.com/trial/nct04938817/

Safety and Efficacy Study of Pembrolizumab in Combination ... This study is a rolling arm study of investigational agents as monotherapy or in combination with pembrolizumab in participants with anti-programmed cell death ...