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 FDA Drug

• 2 other identifiers: 10001536001536-C
• Study Type: interventional
• Target: 16
• 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)

• Determine if there is an increase in CD3+ tumor infiltrating T cells post treatment compared with pre-treatment

  CD3+ tumor infiltrating lymphocytes will be assessed by multiplex immunofluorescence from the surgical/ biopsy tissue collected at week 4-5 and compared with pre-treatment

  4-5 weeks

Secondary Outcomes (4)

• Prolonged Survival

  3-6 months

• Overall Survival

  5 years

• Safety

  Up to 28 days after last treatment

• Determine the rate of increase in TILs by immunohistologyCHANGE TO: Determine the rate of increase in tumor infiltrating lymphocytes (TILs) by immunohistology

  4 weeks CHANGE TO: 4-5 weeks

Study Arms (1)

Arm 1

EXPERIMENTAL

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

Biological: PRGN-2009; Drug: Pembrolizumab

Interventions

PRGN-2009 BIOLOGICAL

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

Arm 1

Pembrolizumab DRUG

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

Arm 1

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 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 HIV, Hepatitis B, or Hepatitis C are eligible if the viral loads are undetectable by quantitative 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-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

Condition Hierarchy (Ancestors)

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

Study Officials

• Charalampos Floudas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

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: October 3, 2025

Record last verified: 2025-10-01

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 are available once genomic data are uploaded per protocol GDS plan for as long as database is active@@@@@@@@@@@@
• Access Criteria: Data from this study may be requested by contacting the PI@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.@@@@@@

Locations

US (1)