Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer

NCT05996523 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 10001536001536-C
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oropharyngeal Squamous Cell Carcinoma (SCC)

Keywords

HPV16/18; PD-1 inhibitor; Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants That Had a 2-fold Increase of Cluster of Differentiation 3 (CD3+) Tumor Infiltrating T Cells in Biopsies Performed Post-treatment Compared to Pre-treatment.

  CD3+ tumor infiltrating T cells post treatment compared with pre-treatment reported with a 95% confidence interval assessed by multiplex CD3+ tumor infiltrating lymphocytes assessed by multiplex immunofluorescence from the surgical/ biopsy tissue collected pre- and post-treatment. The percentage of participants with doubling of baseline CD3+ tumor infiltrating lymphocytes will be provided as well as the 95% confidence interval. The CD3 cells are assessed by multiplex immunofluorescence in the biopsies. Doubling is the desired outcome.

  Pre-Treatment (Baseline) and anytime between Week 4-5 post treatment

Secondary Outcomes (5)

• Overall Survival at 3 Years Compared With Historical Cohort

  3 years

• Overall Survival at 3 Years

  3 years

• Number of Treatment-related Serious Adverse Events (AE) of Grades 1, 2, 3, 4 and/or 5 Along With the AE Term

  From baseline up to 28 days after last treatment, up to 2 months.

• Percentage of 2-fold Increase in Cluster of Differentiation (CD3+) Tumor Infiltrating Lymphocytes (TILs) Post-treatment Compared to Pre-treatment in This Trial Compared to Participants Receiving PRGN2009 in Study NCT04432597

  Pre-Treatment (Baseline) and anytime between Week 4 to 5 post treatment

• Relapse Free Survival (RFS) Rate at 3 Years

  3 years

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Adverse Events were monitored/assessed from the time of first drug administration through 28 days after the last drug administration up to 2 months

Study Arms (1)

Arm 1/PRGN 5x10^11 Viral Particles Subcutaneously Plus Pembrolizumab 200mg Intravenous

EXPERIMENTAL

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

Biological: PRGN-2009; Drug: Pembrolizumab; Diagnostic Test: EKG; Diagnostic Test: CT; Diagnostic Test: PET scan; Diagnostic Test: MRI; Procedure: Biopsy

Interventions

PRGN-2009 BIOLOGICAL

PRGN-2009 5x10\^11 viral particles (VP) subcutaneously (SC) approximately two weeks apart

Arm 1/PRGN 5x10^11 Viral Particles Subcutaneously Plus Pembrolizumab 200mg Intravenous

Pembrolizumab DRUG

Pembrolizumab 200 mg intravenously (IV) concurrently with the first vaccine dose

Also known as: Keytruda

Arm 1/PRGN 5x10^11 Viral Particles Subcutaneously Plus Pembrolizumab 200mg Intravenous

EKG DIAGNOSTIC_TEST

Baseline, completion visit, and safety follow-up visit.

Also known as: Electrocardiogram

Arm 1/PRGN 5x10^11 Viral Particles Subcutaneously Plus Pembrolizumab 200mg Intravenous

CT DIAGNOSTIC_TEST

Screening and baseline (neck and chest), and completion visit (neck).

Also known as: Computed tomography

Arm 1/PRGN 5x10^11 Viral Particles Subcutaneously Plus Pembrolizumab 200mg Intravenous

PET scan DIAGNOSTIC_TEST

Screening and baseline (neck and chest).

Also known as: Positron emission tomography

Arm 1/PRGN 5x10^11 Viral Particles Subcutaneously Plus Pembrolizumab 200mg Intravenous

MRI DIAGNOSTIC_TEST

Screening and baseline (neck and chest), and completion visit (neck).

Also known as: Magnetic resonance imaging

Arm 1/PRGN 5x10^11 Viral Particles Subcutaneously Plus Pembrolizumab 200mg Intravenous

Biopsy PROCEDURE

Baseline and completion visit.

Also known as: Bx

Arm 1/PRGN 5x10^11 Viral Particles Subcutaneously Plus Pembrolizumab 200mg Intravenous

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have cytologically or histologically confirmed newly diagnosed stage I (T1,2 N1), II or III p16-positive oropharyngeal squamous cell carcinoma (SCC) planned for definitive therapy (surgery or chemoradiotherapy).
• Subjects must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Age \>=18 years.
• Eastern Cooperative Oncology Group \[ECOG\] performance status \<= 2.
• Adequate hematologic function at screening, as follows:
• Absolute neutrophil count (ANC) \>=1 x 10\^9/L;
• Hemoglobin (Hgb) \>= 9 g/dL;
• Platelets \>= 75,000/microliter.
• Adequate renal and hepatic function at screening, as follows:
• Serum creatinine \<= 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance \>= 40 mL/min for participant with creatinine levels \> 1.5 x ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl);
• Total bilirubin \<= 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin \<= 3.0 x ULN;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 2.5 x ULN, unless liver metastases are present, then values must be \<= 3 x ULN.
• Participants serologically positive for human immunodeficiency virus (HIV) Hepatitis B, or Hepatitis C are eligible if the viral loads are undetectable by quantitative polymerase chain reaction (PCR). Note: HIV positive participants must have CD4 count \>= 200 cells/mm\^3 at enrollment, be on stable antiretroviral therapy for at least 4 weeks and have no reported opportunistic infections or Castleman's disease within 12 months prior to enrollment.
• Women of child-bearing potential (WOCBP) must agree to use effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 4 months following the last dose of pembrolizumab.
• Participants must be willing to undergo two research biopsies on this study.

You may not qualify if:

• Participants with prior investigational drug, live vaccine, chemotherapy, immunotherapy, or any prior radiotherapy (except for palliative bone directed therapy) within the past 4 weeks prior to the first drug administration. Participants may continue adjuvant hormonal therapy in the setting of a definitively treated cancer (e.g., breast).
• Major surgery within 28 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted).
• Pregnant individuals as evaluated by a positive serum or urine Beta-human chorionic gonadotropin (hCG) at screening
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with the exception of:
• Diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroidism or other mild autoimmune disorders not requiring immunosuppressive treatment.
• Administration of glucocorticoids through a route known to result in a minimal systemic exposure (topical, intranasal, intraocular, or inhalation).
• Systemic (intravenous or oral) glucocorticoid (except for physiologic doses of corticosteroids, i.e., \<= the equivalent of prednisone 10 mg/day) or other immunosuppressors such as azathioprine or cyclosporin A, are excluded because of potential immune suppression. These treatments must be discontinued at least 1 week prior to enrollment for recent short course use (\<= 14 days). Glucocorticoids as premedication for contrast-enhanced studies is allowed prior to enrollment and on study.
• Participants with a prior or concurrent malignancy whose natural history or treatment that has potential to interfere with the safety or efficacy assessment of the regimen.
• Prior allogenic tissue/solid organ transplant.
• Participants with pulse oximetry \< 92% on room air at screening.
• Uncontrolled intercurrent illness that would limit compliance with study requirements suggested by medical history, physical examination or standard clinical assessments such as imaging and laboratory studies.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Electrocardiography; Tomography, X-Ray Computed; Positron-Emission Tomography; Magnetic Resonance Imaging; Biopsy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography; Tomography, Emission-Computed; Radionuclide Imaging; Diagnostic Techniques, Radioisotope; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Charalampos Floudas, DMSc, MS
• Organization: National Cancer Institute

charalampos.floudas@nih.gov

240-474-1575

Study Officials

• Charalampos Floudas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 16, 2023
• First Posted: August 18, 2023
• Study Start: November 7, 2023
• Primary Completion: May 22, 2025
• Study Completion (Estimated): July 16, 2030
• Last Updated: June 23, 2026
• Results First Posted: June 23, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers no sooner than 3 years after the completion of the primary endpoint. Genomic data is available once genomic data is uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Data from this study may be requested by contacting the principal investigator (PI). Genomic data is made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)