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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of pembrolizumab, a monoclonal antibody, in treating leukoplakia, a condition that can cause white patches in the mouth and potentially lead to cancer. Pembrolizumab may stop tumor cells from growing and spreading. Individuals with moderate or severe leukoplakia and measurable lesions that cannot be treated with surgery or radiation may be suitable candidates. The trial aims to determine if pembrolizumab can effectively manage or reduce lesions over six months. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

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.

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

Research has shown that pembrolizumab has been tested in people before. In previous studies, patients tolerated this treatment well, although some experienced side effects. Common side effects involved the mouth, as pembrolizumab can affect oral tissues. However, these side effects did not impact surgical outcomes for those who needed surgery.

The FDA has already approved pembrolizumab for other conditions, indicating a known safety record in different diseases. This approval helps doctors understand its function in the body and what to monitor for safety. While some people do experience unwanted side effects, doctors are familiar with these and can manage them. This trial aims to evaluate how well pembrolizumab works for leukoplakia, a condition that causes white patches in the mouth. Safety information from past studies guides the use of this treatment in new areas like leukoplakia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it leverages the immune system to tackle leukoplakia in a novel way. Unlike traditional treatments that focus on removing lesions through surgery or using topical medications, pembrolizumab is a monoclonal antibody that blocks a protein called PD-1. This mechanism helps unleash the body's immune response to target and potentially reduce leukoplakia lesions. Researchers are excited about this approach because it offers a systemic treatment option that might provide benefits beyond the localized therapies currently available.

What evidence suggests that pembrolizumab might be an effective treatment for leukoplakia?

Research shows that pembrolizumab, a type of medicine, might help treat leukoplakia. This treatment boosts the immune system to fight abnormal cells, potentially stopping their growth and spread. Previous studies on similar conditions have shown good results, with treatments like pembrolizumab slowing disease progression. While specific data on leukoplakia is still being gathered, pembrolizumab's success in other conditions suggests it could be effective. Overall, pembrolizumab aids the immune system by blocking proteins that prevent it from attacking abnormal cells, making it a promising option for this condition. ^{2 6 7 8 9}

Who Is on the Research Team?

Deborah Wong, MD, PhD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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) 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, 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]

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 (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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03603223

Pembrolizumab in Treating Participants With Leukoplakia Study Overview. Brief Summary. This phase II pilot trial studies how well pembrolizumab works in treating leukoplakia. Monoclonal antibodies, such as ...

2. withpower.com withpower.com/trial/phase-3-leukoplakia-oral-4-2019-f12d6

Pembrolizumab for Leukoplakia This trial studies how well pembrolizumab works in treating leukoplakia. Pembrolizumab helps the immune system fight cancer by blocking a protein that prevents ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10654930/

Nivolumab for Patients With High-Risk Oral Leukoplakia Twelve patients (36%) (95% CI, 20.4%-54.8%) had a response by composite score (3 MRs [9%]), 4 had progressive disease (>10% composite score ...

4. aacrjournals.org aacrjournals.org/cancerrescommun/article/1/1/30/363427/Comprehensive-Immunoprofiling-of-High-Risk-Oral

Comprehensive Immunoprofiling of High-Risk Oral ... Our data provide a strong preclinical rationale for the use of PD-1/L1 blockade as oral preventative immunotherapy among patients with high-risk proliferative ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7555729/

Leukoplakia and Immunology: New Chemoprevention ... Personalized, Randomized, Phase 2 Study of Pembrolizumab (MK-3475) for High Risk Oral Intra-Epithelial Neoplasias (Clinical Trials) M.D. Anderson Cancer ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10571987/

Immunotherapy-Related Oral Adverse Effects This paper characterizes the immunotherapy-related adverse effects in the oral tissues, in a large series of patients.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9973379/

Comprehensive Immunoprofiling of High-Risk Oral ... Our data provide a strong preclinical rationale for the use of PD-1/L1 blockade as oral preventative immunotherapy among patients with high-risk proliferative ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

9. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2811991

Nivolumab for Patients With High-Risk Oral Leukoplakia A response rate of 25% was targeted when considering the cumulative risk of serious irAEs. Secondary end points included safety and cancer-free ...