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

NCT05799144 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: VICCHN2208NCI-2023-02083
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Metastatic Oropharyngeal Carcinoma; Recurrent Oropharyngeal Carcinoma

Outcome Measures

Primary Outcomes (4)

• Objective response rate (ORR)

  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.

  Up to approximately 1 year

• Disease control rate (DCR)

  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.

  Up to approximately 1 year

• Progression-free survival (PFS)

  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.

  Up to approximately 1 year

• Overall survival (OS)

  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.

  Up to approximately 1 year

Study Arms (1)

Treatment (pBI-11, TA-HPV, pembrolizumab)

EXPERIMENTAL

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.

Biological: DNA Vaccine; Biological: Human Papillomavirus Tumor Antigen Vaccine; Biological: Pembrolizumab; Procedure: Computed Tomography (CT); Procedure: Magnetic Resonance Imaging (MRI); Procedure: Magnetic Resonance Imaging; Procedure: Biopsy

Interventions

DNA Vaccine BIOLOGICAL

Given pBI-11 IM

Treatment (pBI-11, TA-HPV, pembrolizumab)

Human Papillomavirus Tumor Antigen Vaccine BIOLOGICAL

Given into a muscle

Treatment (pBI-11, TA-HPV, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given into vein

Treatment (pBI-11, TA-HPV, pembrolizumab)

Computed Tomography (CT) PROCEDURE

Undergo a CT

Treatment (pBI-11, TA-HPV, pembrolizumab)

Magnetic Resonance Imaging (MRI) PROCEDURE

Undergo an MRI

Treatment (pBI-11, TA-HPV, pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo blood sample collection

Treatment (pBI-11, TA-HPV, pembrolizumab)

Biopsy PROCEDURE

Undergo tumor biopsy

Treatment (pBI-11, TA-HPV, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent
• Male or female \>= 18 years of age on the day of signing informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Having been diagnosed with R/M p16+ PD-L1 CPS \>= 1 OPC not previously treated for R/M disease. They must be eligible for, and planning to start therapy with pembrolizumab, according to standard of care
• hrHPV(+) status (staining with p16 is adequate) and PD-L1 expression (CPS≥1) in tumor based on validated testing methods performed on FFPE tumor tissue (needle core biopsy or resection; fine needle aspiration/biopsy \[FNA\] cell blocks acceptable if with adequate tissue) at local labs or VUMC labs. \[This biopsy tissue will also be used for the pre-treatment tissue research correlate studies.\] For patients with neither existing tumor hrHPV and PD-L1 CPS test results nor adequate archived tissue available for PD-L1 and hrHPV testing, a biopsy performed during screening is necessary to obtain diagnostic tissue. If no tissue is available for PD-L1 and hrHPV testing on either archived or newly obtained tissue, the patient cannot be enrolled.
• Evaluable tumor burden (measurable and/or non-measurable tumor lesion\[s\]) which can be followed by computed tomography (CT) scan or magnetic resonance imaging (MRI), based on Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by the local site investigator/radiology. Tumors that are biopsied (for diagnosis and research use) will not be considered in the iRECIST version (v)1.1 assessment. However, if patient has only one evaluable tumor, patient may still be eligible for participation
• Absolute neutrophil count (ANC) \>= 1,000/uL (resulted =\< 28 days prior to first dose of protocol-indicated treatment)
• CD4 T cell count \> 200/uL (resulted =\< 28 days prior to first dose of protocol-indicated treatment)
• Platelets \>= 75,000/uL (resulted =\< 28 days prior to first dose of protocol-indicated treatment)
• Hemoglobin \>= 7.0 g/dL (resulted =\< 28 days prior to first dose of protocol-indicated treatment)
• Estimated glomerular filtration rate (eGFR) \>= 45 mL/min (as calculated by the Cockcroft-Gault Formula or calculated/measured by an alternative established institutional standard consistently applied across participants at the site) (resulted =\< 28 days prior to first dose of protocol-indicated treatment)
• Total bilirubin =\< 1.5 times institutional upper limit of normal (ULN), or direct bilirubin =\< ULN for participants with total bilirubin \> 1.5 x ULN (resulted =\< 28 days prior to first dose of protocol-indicated treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 times institutional ULN (resulted =\< 28 days prior to first dose of protocol-indicated treatment)
• Calcium =\< 11.5 mg/dL or =\< 2.9 mmol/L; in patients with albumin outside the normal range, calcium (corrected for albumin) must be =\< 11.5 mg/dL or =\< 2.9 mmol/L (resulted =\< 28 days prior to first dose of protocol-indicated treatment)
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 times institutional ULN; except for patients receiving anticoagulant therapy as long as PT in such patients per investigator judgment is within therapeutic range of intended use of anticoagulants (resulted =\< 28 days prior to first dose of protocol-indicated treatment)

You may not qualify if:

• Disease that can be treated with curative intent as assessed by patient's study physician. If patient in this situation wishes for treatment with palliative intent then they may enroll
• Multiple primary oropharyngeal (OP) tumors
• Primary cancer not originated from the oropharynx
• Has received any therapy for R/M disease. Therapy in the setting of curative intent is allowed
• Patient is pregnant or breastfeeding
• Prior prophylactic or therapeutic vaccination with any human papillomavirus (HPV) antigen except L1
• \* Note: previous receipt of the Gardasil (registered trademark) vaccine (including Gardasil 9 \[registered trademark\]) or the Cervarix (registered trademark) vaccine does not exclude
• Has received a live vaccine within 30 days prior to first dose of study treatment
• Examples of prohibited live vaccines include, but are not limited to measles, mumps, rubella, varicella (chickenpox), zoster (shingles; Zostavax \[registered trademark\] \[not including Shingrix (registered trademark)\]), yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine
• Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist \[registered trademark\] Quadrivalent) are live attenuated vaccines and are not allowed. The three United States (US) FDA-approved coronavirus disease 2019 (COVID-19) vaccines (by Pfizer BioNTech, Moderna, and Janssen) and AstraZeneca COVID-19 vaccine are based on messenger (m)RNA or replication-deficient adenoviral vectors and are allowed
• Is currently participating in or, within 4 weeks prior to first dose of study treatment, has participated in a study of an investigational agent or has used an investigational device
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
• Patients with persistent toxicities of =\< grade 3 (National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) will be excluded
• Diagnosis of immunodeficiency
• Known additional malignancy that is non-localized or progressing or has required active treatment within the past 3 years prior to first dose of study treatment

Sponsors & Collaborators

• Michael K. Gibson: lead

Study Sites (2)

University of Alabama Birmingham

Birmingham, Alabama, 35249, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Vaccines, DNA; human papillomavirus vaccine, TA; pembrolizumab; Magnetic Resonance Spectroscopy; Biopsy

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; Antigens; Biological Factors; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Michael Gibson, MD, PhD

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanderbilt-Ingram Services for Timely Access

CONTACT

800-811-8480; cip@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: April 5, 2023
• Study Start: May 16, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: October 22, 2025

Record last verified: 2025-10

Locations

US (2)