Vaccines + Pembrolizumab for Oropharyngeal Cancer

Recruiting at 1 trial location

Overseen By Vanderbilt-Ingram Services for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Michael K. Gibson

Must be taking: Pembrolizumab

Must not be taking: Live vaccines, Immunosuppressive drugs

Disqualifiers: Pregnancy, Immunodeficiency, Active 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

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 1 year

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two vaccines, pB1-11 and TA-HPV, in combination with the immunotherapy drug pembrolizumab, for treating oropharyngeal cancer, a type of throat cancer linked to HPV. Researchers seek to determine if these vaccines, alongside pembrolizumab, can enhance the immune system's ability to combat cancer that has returned or spread. Participants should have oropharyngeal cancer that is both PD-L1 and HPV positive and should not have received prior treatment for their recurrent or metastatic disease. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive drugs or have received a live vaccine recently, you may need to stop or adjust those treatments before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments tested in this trial—pBI-11, TA-HPV, and pembrolizumab—have been studied for safety in other research.

For pBI-11, earlier studies found that this DNA vaccine can enhance specific immune cells to fight HPV. These studies reported no major safety issues, indicating it is generally well-tolerated.

TA-HPV, another vaccine in this trial, derives from a virus used in smallpox vaccines, which have been safely used for a long time. While vaccines can have side effects, serious ones are rare. The HPV vaccine is known to be safe and effective in preventing HPV-related infections, which is promising for TA-HPV's safety.

Pembrolizumab is already approved by the FDA for several cancers, including head and neck cancer. Research has shown it is generally safe, with no new safety concerns found recently. Most side effects are mild to moderate.

Overall, these treatments are considered well-tolerated based on previous research and approvals. The trial's phase also ensures that safety data is carefully monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for oropharyngeal cancer, which often include surgery, radiation, and chemotherapy, this new approach combines vaccines pBI-11 and TA-HPV with pembrolizumab, an immunotherapy drug. Researchers are excited because these vaccines aim to boost the immune system's ability to recognize and attack cancer cells more effectively. Additionally, pembrolizumab blocks a protein called PD-1, which can help the immune system stay active against cancer cells. This combined approach could potentially enhance the body's natural defenses, offering a more targeted and less invasive treatment option.

What evidence suggests that this trial's treatments could be effective for oropharyngeal cancer?

In this trial, participants will receive a combination of treatments, including pembrolizumab, a type of immunotherapy. Studies have shown that pembrolizumab can help people with head and neck cancers, including oropharyngeal cancer, live longer, especially when the cancer expresses a specific protein called PD-L1. The treatment regimen also includes the pBI-11 vaccine, which research shows can help the immune system fight tumors caused by HPV, and the TA-HPV vaccine, designed to encourage the immune system to attack cancer cells caused by HPV. Using these vaccines with pembrolizumab could potentially enhance the immune system's effectiveness against cancer cells more than pembrolizumab alone. Early studies suggest that this combination might improve the body's ability to fight HPV-related oropharyngeal cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Michael Gibson

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

Adults (18+) with recurrent or metastatic PD-L1 CPS≥1, hrHPV+ oropharyngeal cancer who haven't been treated for this advanced stage. They must have a good performance status, adequate organ function, and not be pregnant or breastfeeding. Participants should agree to use contraception and not donate blood/sperm during the trial.

Inclusion Criteria

Calcium =< 11.5 mg/dL or =< 2.9 mmol/L

Able to father children and sexually active with a WOCBP must agree to use acceptable contraception

aPTT or PTT =< 1.5 times institutional ULN

Exclusion Criteria

My condition can be treated with the goal of curing it.

Pregnant or breastfeeding

My side effects from previous treatments are not severe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pBI-11 vaccine IM, TA-HPV vaccine IM, and pembrolizumab IV. Patients undergo CT or MRI and blood sample collection.

Up to approximately 1 year

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• pBI-11
• Pembrolizumab
• TA-HPV

Trial Overview The trial is testing pBI-11 & TA-HPV vaccines combined with pembrolizumab against HPV-positive oropharyngeal cancer. It aims to see if these treatments together boost the immune system more effectively than pembrolizumab alone in fighting cancer.

How Is the Trial Designed?

Group I: Treatment (pBI-11, TA-HPV, pembrolizumab) Experimental Treatment 7 Interventions

Patients receive pBI-11 vaccine IM, TA-HPV vaccine IM, and pembrolizumab IV on study. Patients undergo CT or MRI and blood sample collection during screening and on study. Patients may undergo tumor biopsy during screening and on study.

Who Is Running the Clinical Trial?

Michael K. Gibson

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

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]

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 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]

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 preclinical model of HPV+ oropharyngeal cancer, combining PD-1 blockade with CTLA-4 inhibition resulted in a remarkable 93.3% survival rate in mice with tongue tumors over a 100-day study, indicating a highly effective immunotherapy strategy.

The addition of a STING agonist to the treatment regimen not only enhanced the efficacy of PD-1 and CTLA-4 blockade but also led to sustained tumor regression in 71% of mice with metastatic disease, highlighting a promising approach for patients who do not respond to standard PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting interferon signaling and CTLA-4 enhance the therapeutic efficacy of anti-PD-1 immunotherapy in preclinical model of HPV+ oral cancer. Dorta-Estremera, S., Hegde, VL., Slay, RB., et al.[2020]

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 with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

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]

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]

Pembrolizumab, an FDA-approved monoclonal antibody for recurrent or metastatic head and neck cancers, has shown limited efficacy, highlighting the need for alternative treatments.

Therapeutic vaccination is emerging as a promising strategy in head and neck cancers, with ongoing research into its potential synergistic effects when combined with anti-PD(L)1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine-Based Immunotherapy for Head and Neck Cancers. Beyaert, S., Machiels, JP., Schmitz, S.[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]

In a phase Ib/IIa study involving 35 patients with recurrent/metastatic HPV-16/18-associated head and neck cancer, the combination of the DNA vaccine MEDI0457 and the PD-L1 inhibitor durvalumab showed an objective response rate of 27.6%, indicating some effectiveness in enhancing HPV-specific T-cell responses.

The treatment was generally well tolerated, with 80% of patients experiencing treatment-related adverse events, mostly mild to moderate, and a median overall survival of 29.2 months, suggesting potential clinical benefit despite not meeting the primary efficacy endpoint.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of MEDI0457 plus Durvalumab in Patients with Human Papillomavirus-Associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma. Aggarwal, C., Saba, NF., Algazi, A., et al.[2023]

HPV-positive tumors account for a significant portion of oropharyngeal squamous cell carcinomas (OSCC), with HPV-16 being the most common high-risk genotype, highlighting the importance of HPV in the development of these cancers.

Current treatment strategies for HPV-induced head and neck squamous cell carcinomas are shifting towards de-escalation, and new immunotherapy approaches are being explored to enhance the immune response against these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An updated overview of HPV-associated head and neck carcinomas. Zaravinos, A.[2022]

Citations

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

The clinical outcome of pembrolizumab for patients with ... However, pembrolizumab plus cetuximab had a higher ORR in patients receiving first-line therapy(47.1%vs40%). And there was no more than level 3 ...

2. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%). In KEYNOTE⁠-⁠671, adverse reactions ...

3. 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+ ... Among the CPS ≥1 population, median EFS was 59.7 months (95% CI, 37.9-not reached) in the KEYTRUDA arm versus 29.6 months (95% CI, 19.5-41.9) in ...

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

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02508

Updated Results of the Phase III KEYNOTE-048 Study Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048.

6. keytruda.com keytruda.com/head-and-neck-cancer/clinical-trial-results-with-chemotherapy/

KEYTRUDA used with chemotherapy as first treatment Half of the people who received KEYTRUDA and chemotherapy were alive without their cancer spreading, growing, or getting worse at 4.9 months, compared to 5.1 ...

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 ... KEYNOTE-689 is the first Phase 3 trial to demonstrate statistically significant and clinically meaningful improvement in EFS in the intent-to-treat population.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02358031

NCT02358031 | A Study of Pembrolizumab (MK-3475) for ... Per protocol, response/progression or adverse events (AEs) that occur during the second pembrolizumab course will not be counted towards efficacy outcome ...