Pembrolizumab for Respiratory Papillomatosis

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Pembrolizumab, a drug that aids the immune system in fighting diseases, as a potential treatment for Recurrent Respiratory Papillomatosis (RRP). RRP causes non-cancerous tumors to grow in the airways, affecting breathing and often requiring repeated surgeries. The trial seeks participants with RRP who have undergone at least three surgeries in one year to remove tumors from the larynx (voice box). The goal is to determine if Pembrolizumab can reduce the need for frequent surgeries and improve breathing. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Pembrolizumab is likely to be safe for humans?

Research shows that patients generally tolerate pembrolizumab well. Most side effects are mild to moderate, making symptoms easy to manage. Importantly, no severe side effects appeared even at higher doses, suggesting the treatment is safe at various levels. Pembrolizumab's safety profile is strong. The FDA has approved it for other uses, further supporting its safety in humans. However, as with any treatment, risks exist, and some patients may experience different reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about pembrolizumab for respiratory papillomatosis because it represents a novel approach by using an immune checkpoint inhibitor. Most treatments for this condition involve surgical removal of papillomas or laser therapy, which only address the symptoms without tackling the underlying cause. Pembrolizumab, on the other hand, works by blocking the PD-1 pathway, helping the immune system recognize and fight the virus causing the papillomas. This mechanism offers the potential for longer-lasting control of the disease, reducing the need for repeated surgeries.

What evidence suggests that Pembrolizumab might be an effective treatment for Recurrent Respiratory Papillomatosis?

Research has shown that pembrolizumab, a type of immune therapy, may help treat recurrent respiratory papillomatosis (RRP). This treatment has effectively managed other conditions related to the human papillomavirus (HPV). For instance, in a study with patients who had recurrent cervical cancer, 36% experienced positive results with pembrolizumab. Since RRP is also connected to HPV, similar benefits might be observed. Pembrolizumab helps the immune system find and attack virus-infected cells, potentially slowing papilloma growth. Early results suggest it might benefit patients with severe RRP affecting the voice box, windpipe, and lungs. ^{2 3 6 7 8}

Who Is on the Research Team?

Sara Pai, MD PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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

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

My blood counts are within normal ranges.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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, 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, 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]

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 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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.2590

A phase II study of pembrolizumab for HPV-associated ... Patient-reported outcomes (PROs) from a phase II trial of pembrolizumab for HPV-associated papilloma patients with laryngeal, tracheal and/or ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.6080

Patient-reported outcomes (PROs) from a phase II trial of ... RRP proliferates in the respiratory tract impacting breathing, swallowing, and voice and carries a 1-4% risk of malignant transformation.There ...

3. ijmdc.com ijmdc.com/index.php?fulltxt=229509&fulltxtj=51&fulltxtp=51-1732089238.pdf

Effectiveness of immunotherapy in recurrent respiratory ... Outcomes after human papillomavirus vaccination in patients with recurrent respiratory papillomatosis: a nonrandomized clinical trial. JAMA ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11821913/

DNA immunotherapy for recurrent respiratory papillomatosis ... Here, we report full study results from a DNA-based therapy in development for RRP from a completed Phase 1/2 trial demonstrating the safety, ...

5. withpower.com withpower.com/trial/phase-3-respiratory-tract-infections-3-2016-1f61d

Pembrolizumab for Respiratory Papillomatosis In a study of 11 heavily pretreated patients with recurrent cervical cancer, pembrolizumab demonstrated a clinical benefit rate of 36%, with 18% of patients ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02570-5/fulltext

992O Pembrolizumab for HPV-associated recurrent ... Up to 8.9% of patients with RRP have pulmonary involvement, which carries a 32-fold increased lifetime risk of malignant transformation. Repeat surgical or ...

7. fda.gov fda.gov/news-events/press-announcements/fda-approves-first-immunotherapy-recurrent-respiratory-papillomatosis

FDA Approves First Immunotherapy for Recurrent ... The safety profile was favorable, with most treatment-emergent adverse events being mild to moderate. No dose-limiting toxicities were observed, ...

8. medicine.yale.edu medicine.yale.edu/news-article/yale-surgeon-scientist-secures-fda-orphan-drug-designation-for-pembrolizumab-in-rare-respiratory-disease/

Yale Surgeon-Scientist Secures FDA Orphan Drug ... Sara Pai, MD, PhD, has achieved FDA orphan drug designation for pembrolizumab to treat recurrent respiratory papillomatosis (RRP), a rare and