Pembrolizumab for Leukoplakia

Recruiting at 2 trial locations

Overseen By Thu P Ly

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Immunosuppressants, Steroids, Monoclonal antibodies, others

Disqualifiers: Active infection, Autoimmune disease, HIV, 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: 33

Duration: 6 months

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how well pembrolizumab works in treating leukoplakia. Pembrolizumab helps the immune system fight cancer by blocking a protein that prevents immune cells from attacking cancer cells. The trial targets patients with leukoplakia, aiming to see if this medication can effectively treat this condition. Pembrolizumab is an immune checkpoint inhibitor that has been used in the treatment of various cancers, including non-small cell lung cancer, melanoma, and head and neck cancers.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these medications before starting the trial.

How is the drug pembrolizumab unique for treating leukoplakia?

Pembrolizumab is unique because it is an immunotherapy drug that works by blocking the PD-1 receptor on T cells, which helps the immune system attack abnormal cells. This mechanism is different from traditional treatments for leukoplakia, which often involve surgical removal or topical treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the drug pembrolizumab for leukoplakia?

Pembrolizumab has shown effectiveness in treating various cancers, such as non-small cell lung cancer and melanoma, by targeting the PD-1/PD-L1 pathway, which helps the immune system attack cancer cells. While there is no direct evidence for leukoplakia, its success in other conditions suggests potential benefits. ^{1 3 4 5 6}

Research Team

Deborah Wong, MD, PhD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with moderate to severe dysplasia or carcinoma in situ within oral leukoplakia lesions that can't be removed surgically or treated with radiation, or for those who refuse such treatments. Participants must have measurable lesions, provide consent for photographs and biopsies, and meet specific health criteria including blood counts and organ function tests. Women of childbearing potential must use contraception.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Absolute neutrophil count (ANC) >= 1,500 /mcL within 10 days of treatment initiation

I can provide a biopsy sample or am willing to have a new biopsy for the study.

Exclusion Criteria

I haven't had cancer treatment with a monoclonal antibody in the last 4 weeks or have recovered from its side effects.

I haven't had cancer treatment in the last 2 weeks or I've recovered from its side effects.

I do not have mild dysplasia or hyperplasia with my leukoplakia or erythroleukoplakia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously over 30 minutes on day 1. Courses repeat every 3 weeks for 6 months in the absence of disease progression or unacceptable toxicity.

6 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

At 30 days and every 3 months

Treatment Details

Interventions

• Pembrolizumab

Trial Overview The study is testing the effectiveness of pembrolizumab, a monoclonal antibody designed to block tumor growth by interfering with certain proteins on cells. This phase II pilot trial aims to see how well it works against leukoplakia by potentially preventing the abnormal cells from growing and spreading.

Participant Groups

Group I: Treatment (pembrolizumab) Experimental Treatment 1 Intervention

Participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for 6 months in the absence of disease progression or unacceptable toxicity.

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?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

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, 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 anti-PD-1 antibody used for treating various cancers, can cause immune-related adverse events (IRAEs) affecting multiple body systems, including rare oral mucosal issues like glossitis.

In a case study of a 71-year-old male with lung cancer, treatment with oral prednisone effectively improved tongue ulcerations caused by pembrolizumab, highlighting the need for awareness of such rare side effects and their management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-Induced Immune-Mediated Glossitis. Alias, A., Hall, JA., Kulkarni, 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]

Pembrolizumab (Keytruda), an immunotherapy drug used for various cancers, can lead to immune-related adverse events, including severe oral lichenoid lesions, as seen in a case study of a 65-year-old female with bladder cancer.

This case is notable as it is the first documented instance of a biopsy-proven oral erosive lichenoid reaction linked to pembrolizumab, confirmed through direct immunofluorescence, highlighting the need for awareness of such complications in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe oral erosive lichenoid reaction to pembrolizumab therapy. Bhattacharyya, I., Chehal, H., Migliorati, C.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

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 thoracic malignancies: current landscape and future directions. [2017]

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

Pembrolizumab-Induced Immune-Mediated Glossitis. [2022]

3. 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]

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

Severe oral erosive lichenoid reaction to pembrolizumab therapy. [2022]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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