Pembrolizumab for Oral Cancers

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Steroids

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: 10

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of pembrolizumab, a type of immunotherapy, for individuals with high-risk oral intraepithelial neoplasia, a condition that can progress to oral cancer. Immunotherapy enhances the immune system's ability to attack cancer cells, potentially preventing their growth and spread. Participants will either receive pembrolizumab or undergo observation without treatment to compare outcomes. This trial suits those diagnosed with oral intraepithelial neoplasia who have specific genetic markers or a history of oral cancer. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 any form of immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment.

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

Research has shown that pembrolizumab is generally safe and well-tolerated. Previous studies found its side effects manageable and similar to those observed in earlier treatments. Importantly, no new safety issues emerged, indicating that the risks were as expected. This suggests that pembrolizumab is relatively safe to use, with predictable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for oral cancers?

Pembrolizumab is unique because it is an immunotherapy drug that works by targeting and blocking the PD-1 pathway, a mechanism that cancer cells often exploit to evade the immune system. Unlike traditional treatments for oral cancers, such as surgery, radiation, or chemotherapy, pembrolizumab harnesses the body's own immune system to recognize and fight cancer cells more effectively. Researchers are excited about pembrolizumab because it offers a new approach that could provide better outcomes with potentially fewer side effects compared to conventional therapies.

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

Research shows that pembrolizumab might help treat oral cancers. In this trial, some participants will receive pembrolizumab, an immunotherapy that aids the immune system in identifying and attacking cancer cells. Studies have found that adding pembrolizumab to treatment plans for head and neck cancers, including oral cancers, can improve outcomes. Early research demonstrated that pembrolizumab can slow the growth and spread of these cancer cells. The FDA has approved pembrolizumab for certain head and neck cancers, supporting its potential effectiveness. This evidence suggests that pembrolizumab might help control high-risk oral cell changes and possibly prevent them from becoming cancerous. Meanwhile, other participants in this trial will undergo observation without receiving pembrolizumab. ^{1 4 5 6 7}

Who Is on the Research Team?

Renata Ferrarotto

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with high-risk oral intraepithelial neoplasia, confirmed by biopsy within the last year. Participants must have certain genetic markers (LOH at specific chromosomal sites), be in good health based on blood counts and liver function tests, and not be pregnant or breastfeeding. They should agree to use contraception during the study period.

Inclusion Criteria

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN

I am using two birth control methods or am not having sex to join this study.

Absolute neutrophil count >= 1,500/mcL

Exclusion Criteria

I have been treated with drugs targeting PD-1, PD-L1, or PD-L2.

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously every 21 days for up to 4 courses

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Visits at 6, 9, 12, 18, 24, 30, and 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial is testing pembrolizumab, an immunotherapy drug that may help the immune system fight cancer cells in patients with a high risk of developing oral cancer. The study will compare patient outcomes between those receiving pembrolizumab and those under observation.

How Is the Trial Designed?

Group I: Arm B (pembrolizumab) Experimental Treatment 2 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (observation) Active Control 1 Intervention

Patients undergo observation.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[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]

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, 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) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10910039/

The clinical outcome of pembrolizumab for patients with ... In 2021, there were 148,000 newly diagnosed cases of HNSCC, and regrettably, 78,000 patients succumbed to the disease (1). Squamous cell ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... The addition of pembrolizumab to established neoadjuvant and adjuvant regimens led to significant improvement in efficacy outcomes in phase 3 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02882282?cond=cancer&aggFilters=status%3A%2Cresults%3Awith%2Cphase%3A

Pembrolizumab in Treating Patients With High Risk Oral ... This randomized phase II trial studies how well pembrolizumab works in treating patients with high risk oral intraepithelial neoplasia.

4. merck.com merck.com/news/fda-approves-keytruda-pembrolizumab-for-pd-l1-resectable-locally-advanced-head-neck-squamous-cell-carcinoma-as-neoadjuvant-treatment-continued-as-adjuvant-treatment-combined-with-radiother/

FDA Approves KEYTRUDA® (pembrolizumab) for PD-L1+ ... These data include cancers of the oral cavity, pharynx and larynx. Most head and neck cancer is squamous cell carcinoma which begins in the flat ...

5. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) Health care professionals may review efficacy data for KEYTRUDA® (pembrolizumab), browse the indications and select the corresponding KEYNOTE trials for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9902012/

Updated Results of the Phase III KEYNOTE-048 Study - PMC The safety profile of pembrolizumab alone was favorable versus cetuximab-chemotherapy and was similar for pembrolizumab-chemotherapy and ...

7. merck.com merck.com/news/mercks-keytruda-pembrolizumab-met-primary-endpoint-of-event-free-survival-efs-as-perioperative-treatment-regimen-in-patients-with-resected-locally-advanced-head-and-neck-squamous-c/

Merck's KEYTRUDA® (pembrolizumab) Met Primary ... The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were identified.