HPV Vaccine + Pembrolizumab for Oropharyngeal Cancer

Overseen By Charalampos Floudas, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Glucocorticoids, Immunosuppressors

Disqualifiers: Pregnancy, Autoimmune disease, 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

Compensation: Varies

Number of Visits: 7

29 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Cancers in and around the mouth associated with human papilloma virus (HPV) are common. Two treatments (the drug pembrolizumab and the HPV vaccine PRGN-2009) have been shown to work well when used individually against these cancers. Researchers want to find out if they might work better when used together. Objective: To test pembrolizumab combined with PRGN-2009 in people with HPV-positive cancers in and around the mouth. Eligibility: Adults aged 18 and older newly diagnosed with HPV-positive cancers in and around the mouth. Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans. They may need to have a biopsy: A sample of tissue will be taken from the tumor. PRGN-2009 is given as an injection under the skin. Pembrolizumab is given through a tube attached to a needle inserted into a vein in the arm. Participants will have at least 3 clinic visits: At the first, they will receive both the drug and the vaccine; 15 days later, they will receive a second shot of the vaccine. At the third visit, about 1 week after the second, they will have follow-up tests. During these visits, participants will give samples of blood, urine, and saliva. Imaging scans and biopsies will be repeated. They will have tests of their heart function. Participants may opt to return for another follow-up visit about 1 month after their second dose of the vaccine. Participants will have follow-up contacts by phone 3 and 6 months after starting the study. The calls will continue once a year for 5 years.

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 glucocorticoids or other immunosuppressive drugs, you must stop them at least 1 week before joining the study. You can continue adjuvant hormonal therapy if you have a definitively treated cancer.

What data supports the effectiveness of the drug pembrolizumab for oropharyngeal cancer?

Pembrolizumab has been shown to be effective in treating head and neck squamous cell carcinoma (HNSCC), with an objective response rate of 16% and some patients experiencing long-lasting responses. This suggests it may also be beneficial for oropharyngeal cancer, which is a type of HNSCC. ^{1 2 3 4 5}

Is the combination of HPV Vaccine and Pembrolizumab safe for treating oropharyngeal cancer?

Pembrolizumab, also known as Keytruda, has been used in various studies for head and neck cancers, showing some serious side effects like pneumonia, skin issues, and thyroid problems, but it is generally considered to have an acceptable safety profile. It has been approved for use in similar conditions, and while it can cause immune-related side effects, these are manageable with proper care. ^{1 3 5 6 7}

What makes the HPV Vaccine + Pembrolizumab treatment unique for oropharyngeal cancer?

This treatment is unique because it combines the HPV vaccine with pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, potentially offering a novel approach for oropharyngeal cancer, which is often linked to HPV infection. Pembrolizumab has shown effectiveness in other head and neck cancers, but combining it with an HPV vaccine could enhance its effectiveness specifically for HPV-related cancers. ^{1 2 3 4 5}

Research Team

Charalampos Floudas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with newly diagnosed HPV-positive oropharyngeal cancer, who are planning standard treatment and can sign consent. They must be willing to undergo biopsies, have measurable disease, and meet certain health criteria including HIV, Hepatitis B/C status. Women must agree to use contraception.

Inclusion Criteria

Subjects must have measurable disease, per RECIST 1.1

Ability to understand and willingness to sign a written informed consent document

Adequate hematologic function at screening: ANC >=1 x 10^9/L, Hgb >= 9 g/dL, Platelets >= 75,000/microliter

Exclusion Criteria

I have had a transplant of tissue or an organ from another person.

I am currently taking certain steroids or drugs that suppress my immune system.

Pregnant individuals

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction/Neoadjuvant Therapy

Participants receive PRGN-2009 and pembrolizumab before definitive treatment

4-5 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up contacts by phone at 3 and 6 months, then annually

Long-term Follow-up

Assess overall survival and recurrence-free survival once a year for 5 years

5 years

Treatment Details

Interventions

• Pembrolizumab
• PRGN-2009

Trial Overview The trial is testing the combination of an immunotherapeutic HPV vaccine (PRGN-2009) with Pembrolizumab before standard cancer treatments in patients with HPV-associated mouth cancers. It involves injections and infusions followed by multiple clinic visits for monitoring.

Participant Groups

Group I: Arm 1 Experimental Treatment 2 Interventions

PRGN 5x10\^11 Viral Particles (VP) SC plus pembrolizumab 200mg IV as induction/ neoadjuvant therapy

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

In a study of 257 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treated with pembrolizumab, biomarkers such as tumor mutational burden (TMB), PD-L1 expression, and T-cell-inflamed gene expression profile (Tcellinf GEP) were found to be significantly associated with overall response rates (ORR) to the treatment.

The study indicated that higher levels of these biomarkers correlated with better treatment responses, suggesting that they could be useful in predicting how well patients will respond to pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers predictive of response to pembrolizumab in head and neck cancer. Pfister, DG., Haddad, RI., Worden, FP., et al.[2023]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

In a study of 36 patients with resectable HPV-unrelated head and neck squamous-cell carcinoma, neoadjuvant pembrolizumab was found to be safe, with no serious adverse events reported during treatment.

The treatment resulted in a pathologic tumor response in 44% of patients, and the one-year relapse rate for those with high-risk pathology was significantly lower at 16.7%, compared to the historical rate of 35%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Uppaluri, R., Campbell, KM., Egloff, AM., et al.[2021]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

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 has been approved by the FDA as the first-line treatment for both HPV-positive and HPV-negative recurrent head and neck squamous cell carcinoma, marking it as a significant advancement in immunotherapy for this cancer type.

The approval allows pembrolizumab to be used either alone for tumors expressing PD-L1 or in combination with chemotherapy, highlighting the need for healthcare providers to be aware of and manage potential immune-related toxicities such as dermatitis and mucositis associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Immune-Related Dermatitis and Mucositis Associated With Pembrolizumab in Metastatic Human Papillomavirus-Associated Squamous Cell Carcinoma of the Oropharynx. Fazer, C., Price, KA.[2021]

References

1. England 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. [2019]

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

Biomarkers predictive of response to pembrolizumab in head and neck cancer. [2023]

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

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. [2022]

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

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Management of Immune-Related Dermatitis and Mucositis Associated With Pembrolizumab in Metastatic Human Papillomavirus-Associated Squamous Cell Carcinoma of the Oropharynx. [2021]