Neoplasms

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Mouth and Tooth Diseases

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Oropharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

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Otorhinolaryngologic Diseases

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Pembrolizumab

Vaccines

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Antineoplastic Agents, Immunological

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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.

DNA Vaccine

Human Papillomavirus Tumor Antigen Vaccine

Computed Tomography (CT)

Magnetic Resonance Imaging (MRI)

Magnetic Resonance Imaging

Biopsy

Vanderbilt-Ingram Services for Timely Access

Vanderbilt-Ingram Service for Timely Access

Michael Gibson, MD, PhD

This phase II trial tests how well pB1-11 and human papillomavirus tumor antigen (TA-HPV) vaccines in combination with pembrolizumab work in treating patients with oropharyngeal cancer that has come back (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic) and that is PD-L1 and human papillomavirus (HPV) positive. Oropharyngeal cancer is a type of head and neck cancer involving structures in the back of the throat (the oropharynx), such as the non-bony back roof of the mouth (soft palate), sides and back wall of the throat, tonsils, and back third of the tongue. Scientists have found that some strains or types of a virus called HPV can cause oropharyngeal cancer. pBI-11 is a circular deoxyribonucleic acid (DNA) (plasmid) vaccine that promotes antibody, cytotoxic T cell, and protective immune responses. TA-HPV is an investigational recombinant vaccina virus derived from a strain of the vaccina virus which was widely used for smallpox vaccination. Vaccination with this TA-HPV vaccine may stimulate the immune system to mount a cytotoxic T cell response against tumor cells positive for HPV, resulting in decreased tumor growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread by inhibiting the PD-1 receptor. These investigational vaccines could cause or enhance an immune response in the body against HPV, during which time the activity of pembrolizumab against oropharyngeal cancer associated with HPV may be strengthened. These drugs in combination may be more effective in increasing the ability of the immune system to fight oropharyngeal cancer than pembrolizumab alone.

PRIMARY OBJECTIVE:

I. To assess the safety and feasibility of intramuscular PVX7 (pBI-11/pBI-11/human papillomavirus tumor antigen vaccine \[TA-HPV\]) immunization in patients with HPV+ recurrent/metastatic (R/M) oropharyngeal carcinoma (OPC) undergoing treatment with pembrolizumab.

SECONDARY OBJECTIVE:

I. To assess the response rate (RR) of the addition of pBI-11 and TA-HPV to pembrolizumab (P) as first line therapy for patients with PD-L1+ (combined positive score \[CPS\] \>= 1), HPV+, R/M OPC.

EXPLORATORY OBJECTIVES:

I. To evaluate the overall survival (OS), progression free survival (PFS) and safety of the combination of PVX7 and pembrolizumab in this population.

II. To evaluate correlates of clinical activity by: (1) comparing HPV16/18 E6/E7-specific cellular and humoral immunity in pre- versus (vs.) post-pBI-11 and TA HPV-treated OPC patients that are pembrolizumab responders (R) and/or non-responders (NR).

OUTLINE:

Patients receive pBI-11 vaccine intramuscularly (IM), TA-HPV vaccine IM, and pembrolizumab intravenously (IV) on study. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection during screening and on study. Patients may undergo tumor biopsy during screening and on study.

pBI-11 & TA-HPV (With Pembrolizumab as Treatment for Patients w/Advanced, PD-L1 CPS≥1, hrHPV+ Oropharyngeal Cancer

An Open-Label Phase II Clinical Trial Assessing the Safety, Feasibility, Efficacy and Immunological Correlates of Heterologous Prime-Boost With pBI-11 (IM) and TA-HPV (IM) Combined With Pembrolizumab as Treatment for Patients With Advanced, PD-L1 CPS≥1, hrHPV+ Oropharyngeal Cancer

The proportion of eligible, response evaluable patients with a best overall response (BOR). Objective response rate will be summarized as proportions of the total number of eligible, response evaluable patients with 95% confidence intervals. Logistic and Cox (proportional hazards) regression will be used to assess the association between important prognostic variables (e.g, gender, age) with objective response rate. Objective response rate will be monitored using Simon's minimax design.

The proportion of eligible, response evaluable patients with a best overall response of complete response, partial response or stable disease. Disease control rate will be summarized as proportions of the total number of eligible, response evaluable patients with 95% confidence intervals.

Estimated using the method of Kaplan and Meier (product limit estimator). Logistic and Cox (proportional hazards) regression will be used to assess the association between important prognostic variables (e.g, gender, age) with progression-free survival. The odds ratio (OR) for response and hazard ratio (HR) for progression-free survival will be presented with 95% confidence intervals as measure of effect size.

Estimated using the method of Kaplan and Meier (product limit estimator). Logistic and Cox (proportional hazards) regression will be used to assess the association between important prognostic variables (e.g, gender, age) with overall survival. The odds ratio for response and hazard ratio for overall survival will be presented with 95% confidence intervals as measure of effect size.

Michael K. Gibson

Associate Professor of Medicine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
pBI-11 & TA-HPV (With Pembrolizumab as Treatment for Patients w/Advanced, PD-L1 CPS≥1, hrHPV+ Oropharyngeal Cancer	NCT05799144	Metastatic Orop... Recurrent Oroph...	DNA Vaccine Human Papilloma... Pembrolizumab Computed Tomogr... Magnetic Resona... Magnetic Resona... Biopsy	18 Years -	Vanderbilt-Ingram Cancer Center
pBI-11 & TA-HPV (With Pembrolizumab as Treatment for Patients w/Advanced, PD-L1 CPS≥1, hrHPV+ Oropharyngeal Cancer	NCT05799144	Metastatic Orop... Recurrent Oroph...	DNA Vaccine Human Papilloma... Pembrolizumab Computed Tomogr... Magnetic Resona... Magnetic Resona... Biopsy	18 Years -	Vanderbilt-Ingram Cancer Center

Spots Global Cancer Trial Database for human papillomavirus tumor antigen vaccine