Pembrolizumab for Respiratory Papillomatosis

Recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: Unknown

Duration: Up to 2 years

21 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before joining the study.

What data supports the effectiveness of the drug pembrolizumab for respiratory papillomatosis?

Pembrolizumab has shown effectiveness in treating cervical cancer, particularly in patients whose tumors express a specific protein called PD-L1. This suggests that pembrolizumab may also be effective in other conditions related to human papillomavirus (HPV), like respiratory papillomatosis, due to its ability to target similar pathways. ^{1 2 3 4 5}

Is pembrolizumab generally safe for humans?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause some immune-related side effects. These include thyroid issues, lung inflammation, and in rare cases, type 1 diabetes. It's important to discuss potential risks with your doctor. ^{2 6 7 8 9}

How is the drug pembrolizumab unique for treating respiratory papillomatosis?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that targets the PD-1 pathway, which helps the immune system recognize and attack abnormal cells. This mechanism is different from traditional treatments for respiratory papillomatosis, which often involve surgical removal of growths. ^{2 7 10 11 12}

What is the purpose of this trial?

This research study is evaluating an immune modulatory agent as a possible treatment for patients with Recurrent Respiratory Papillomatosis (RRP) with significant disease involving the larynx, trachea, and/or lungs. The investigators will be using Pembrolizumab as the treating agent.

Research Team

Sara Pai, MD PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for individuals aged 12 and older with Recurrent Respiratory Papillomatosis (RRP) affecting the larynx, trachea, or lungs. Participants must have had at least three surgeries in a year to remove laryngeal lesions and show adequate organ function. Women of childbearing age must use birth control, and men must agree to contraception during the study.

Inclusion Criteria

My blood counts are within normal ranges.

Absolute neutrophil count (ANC) ≥1,500 /mcL

I agree to use birth control or abstain from sex during and up to 120 days after the study.

Exclusion Criteria

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

You are allergic to pembrolizumab or any of the ingredients in it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pembrolizumab 200 mg as a 30-minute IV infusion every 3 weeks

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years after enrollment of the last patient

Treatment Details

Interventions

• Pembrolizumab

Trial Overview The trial is testing Pembrolizumab as a potential treatment for RRP. This immune modulatory agent aims to help those with significant disease in their airways by possibly reducing the growth of papillomas caused by HPV.

Participant Groups

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Treatment will be administered on Day 1 of each cycle after all procedures/assessments have been completed

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?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Pembrolizumab, an antibody targeting the PD-1 receptor, has shown limited effectiveness as a standalone treatment for recurrent and/or metastatic cervical cancer in the general patient population, but it has received accelerated approval from the FDA for patients with PD-L1-expressing tumors due to its potential for durable responses.

Future research is focusing on combining pembrolizumab with other therapies like chemotherapy and radiotherapy, and identifying additional biomarkers beyond PD-L1 expression will be crucial to better select patients who are likely to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of cervical cancer. Marret, G., Borcoman, E., Le Tourneau, C.[2020]

Pembrolizumab is an FDA-approved immune checkpoint inhibitor specifically targeting the PD-1 receptor, showing promise in treating recurrent or metastatic cervical cancer in patients whose tumors express PD-L1.

Clinical studies suggest that pembrolizumab could become a preferred treatment option for advanced cervical cancer, but further research is needed to identify which patients will benefit the most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced cervical cancer: safety and efficacy. De Felice, F., Giudice, E., Bolomini, G., et al.[2021]

In a study of 11 heavily pretreated patients with recurrent cervical cancer, pembrolizumab demonstrated a clinical benefit rate of 36%, with 18% of patients showing a partial response and another 18% achieving disease stabilization.

The treatment was generally well tolerated, with a median overall survival of 26 weeks and a 6-month survival rate of 65%, indicating promising efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Pembrolizumab in Recurrent Cervical Cancer: Case Series and Review of Published Data. Kranawetter, M., Röhrich, S., Müllauer, L., et al.[2019]

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA as a second-line treatment for recurrent or metastatic cervical cancer in patients with a PD-L1 combined positive score of at least 1.

In a phase II trial, pembrolizumab demonstrated an objective response rate of 14.3%, indicating its potential efficacy in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab OK'd for Cervical Cancer. [2019]

In a phase 3 trial involving 548 patients with PD-L1-positive metastatic cervical cancer, adding pembrolizumab to chemotherapy significantly improved progression-free survival, with a median of 10.4 months compared to 8.2 months for the placebo group.

Overall survival at 24 months was also better in the pembrolizumab group (53.0%) compared to the placebo group (41.7%), indicating that pembrolizumab enhances the effectiveness of chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. Colombo, N., Dubot, C., Lorusso, D., et al.[2023]

A 43-year-old woman developed acute hypoxic respiratory failure shortly after her third infusion of pembrolizumab, a checkpoint inhibitor used for treating recurrent respiratory papillomatosis, highlighting a serious complication of this therapy.

The patient's respiratory failure improved after stopping pembrolizumab and receiving corticosteroids, but her underlying asthma remained poorly controlled, indicating the need for careful monitoring of respiratory function in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Induced Acute Persistent Airway Disease in a Patient with Recurrent Respiratory Papillomatosis (RRP). Marcus, K., Lee, DJ., Wilson, JS., et al.[2022]

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 (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, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., 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]

In a review of 567 reports of immune-mediated necrotizing myopathy (IMNM), 14 cases were associated with pembrolizumab, indicating a significant link between this treatment and the adverse event, with a reporting odds ratio of 17.59.

The study emphasizes the importance of updated diagnostic criteria for IMNM and suggests that better collaboration between oncologists and neurologists is needed to address these neurological complications related to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-mediated necrotizing myopathy with pembrolizumab: a specific neuromuscular entity. Trenque, T., Lepoix, E., Trenque, A., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of cervical cancer. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced cervical cancer: safety and efficacy. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Activity of Pembrolizumab in Recurrent Cervical Cancer: Case Series and Review of Published Data. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab OK'd for Cervical Cancer. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Induced Acute Persistent Airway Disease in a Patient with Recurrent Respiratory Papillomatosis (RRP). [2022]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Immune-mediated necrotizing myopathy with pembrolizumab: a specific neuromuscular entity. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]