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Oropharyngeal Squamous Cell Carcinoma (SCC)Phase 2NCT05996523

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

A Phase 2 study testing PRGN-2009, Pembrolizumab and EKG in people with Oropharyngeal Squamous Cell Carcinoma (SCC), run by National Cancer Institute (NCI) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
What is being tested?
PRGN-2009, Pembrolizumab and EKG
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
7 Nov 2023to 16 Jul 2030
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.
  • Ability of participant to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.

Read more

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.

Read the detailed description

Background

-Human papilloma virus-associated oropharyngeal cancer (HPV-OPC) is the most common HPV-associated malignancy in the United States, with an increasing incidence. Although the prognosis for stage I HPV-OPC is favorable, about 20 percent of patients with stage II

disease and 35 percent of patients with stage III disease will die within four years.

  • The standard-of-care primary treatment for HPV-OPC without distant metastasis is definitive concurrent chemoradiotherapy (primarily) or surgery (which may be followed by adjuvant chemoradiotherapy).
  • Neoadjuvant/induction immunotherapy is in clinical trials aiming to induce antigen-specific immunity prior to primary treatment and to reduce the risk of disease relapse. Pembrolizumab, an anti-PD-1 monoclonal antibody that is Food and Drug Administration (FDA)-approved for first-line treatment of recurrent/metastatic head and neck squamous cell cancer (HNSCC) has been used in these trials and shown to be safe and active.
  • PRGN-2009 is an anti-HPV immunotherapeutic vaccine. It has demonstrated induction of HPV antigen-specific responses and tumor growth inhibition in pre-clinical models of HPV-associated malignancy, with improved anti-tumor efficacy upon addition of T-cell immune checkpoint blockade. In a Phase I/II trial at the National Cancer Institute (NCI) it has demonstrated excellent safety and tolerability as monotherapy or in combination with checkpoint blockade in recurrent/metastatic disease but also as monotherapy in neoadjuvant/induction context for HPV-OPC.

Objective:

-To determine if the use of PRGN-2009 with pembrolizumab in participants with p16-positive OPC can result in a >= 2-fold increase in cluster of differentiation 3 (CD3+) tumor infiltrating T cells post treatment compared with pre-treatment.

Eligibility:

  • Age >= 18 years.
  • Pathologically confirmed newly diagnosed Stage I (T1, T2; N1), II or III p16-positive OPC.

Design:

  • This is a Phase II study to evaluate the effect of PRGN-2009 and pembrolizumab before definitive treatment in subjects with p16-positive OPC.
  • Participants will receive PRGN-2009 and pembrolizumab prior to definitive treatment.
  • Participants will receive two doses of PRGN-2009 5x10^11 viral particles (VP) subcutaneously (SC) approximately two weeks apart, and one dose of pembrolizumab 200 mg intravenously (IV) concurrently with the first vaccine dose.
  • Up to 20 evaluable participants will be enrolled.
Being tested
PRGN-2009, Pembrolizumab, EKG, CT, PET scan
Keywords
HPV16/18, PD-1 inhibitor, Monoclonal Antibody
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PRGN-2009Biological

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

  • PembrolizumabDrug

    Also called Keytruda

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

  • EKGDiagnostic test

    Also called Electrocardiogram

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

  • CTDiagnostic test

    Also called Computed tomography

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

  • PET scanDiagnostic test

    Also called Positron emission tomography

    Screening and baseline (neck and chest).

  • MRIDiagnostic test

    Also called Magnetic resonance imaging

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

  • BiopsyProcedure or surgery

    Also called Bx

    Baseline and completion visit.

Study groups in NCT05996523
Study groupRoleWhat they receive
Arm 1/PRGN 5x10^11 Viral Particles Subcutaneously Plus Pembrolizumab 200mg IntravenousExperimentalPRGN 5x10^11 Viral Particles (VP) subcutaneous (SC) plus pembrolizumab 200mg intravenous (IV) as induction/ neoadjuvant therapy
Receives: Biological: PRGN-2009; Drug: Pembrolizumab; Diagnostic Test: EKG; Diagnostic Test: CT; Diagnostic Test: PET scan; Diagnostic Test: MRI; Procedure: Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (5)

  1. Overall Survival at 3 Years Compared With Historical Cohort

    Assess if PRGN-2009 plus pembrolizumab results in significantly prolonged survival at three years as compared to the expected 80% three-year historical survival in p16-positive oropharyngeal cancer (OPC) participants. Three-year overall survival will be measured using a Kaplan-Meier curve and will be compared descriptively with the historical benchmark. Participants who receive two doses of PRGN-2009 and the single dose of pembrolizumab and go on to receive standard definitive therapy will be evaluable for overall survival assessment.

    Measured: 3 years

  2. Overall Survival at 3 Years

    Overall survival was assessed using the Kaplan-Meier method and is defined as the time from the date of first treatment to the date of death (any cause). Participants who receive two doses of PRGN-2009 and the single dose of pembrolizumab and go on to receive standard definitive therapy will be evaluable for overall survival assessment.

    Measured: 3 years

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

    Number of treatment-related serious adverse events of Grades 1, 2, 3, 4 and/or 5 along with the AE term. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. All participants who receive any investigational treatment will be evaluable for safety and toxicity evaluations.

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

  4. 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

    Percentage of 2-fold increase in CD3+ Tumor Infiltrating Lymphocytes (TILs) by multiplex immunofluorescence post-treatment compared to pre-treatment in participants receiving PRGN2009 plus pembrolizumab in this trial as compared to that in participants receiving PRGN2009 monotherapy in study NCT04432597. Results of the primary endpoint of this study (Proportion of 2-fold increase in CD3+ Tumor Infiltrating Lymphocytes (TILs) by multiplex immunofluorescence post-treatment compared to pre-treatment) were compared with the same in participants in trial NCT04432597 (PRGN-2009 monotherapy). The two percentages will be compared descriptively and reported with a 95% confidence interval.

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

  5. Relapse Free Survival (RFS) Rate at 3 Years

    Relapse free survival was assessed using the Kaplan-Meier method and is defined as the time from completion of standard chemoradiation to the date of disease recurrence or death (any cause) whichever comes first. Participants who receive two doses of PRGN-2009 and the single dose of pembrolizumab and go on to receive standard definitive therapy will be evaluable for relapse-free-survival assessment.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Aug 2023
  2. Study start7 Nov 2023
  3. Primary completion22 May 2025
  4. Study completion16 Jul 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05996523
Sponsor's protocol ID
10001536
Other IDs
001536-C
Status last verified
Jun 2026
First submitted
16 Aug 2023
Last updated
23 Jun 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All collected individual participant data (IPD) will be shared. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PRGN-2009, Pembrolizumab and EKG in people with Oropharyngeal Squamous Cell Carcinoma (SCC), run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Pre-Treatment (Baseline) and anytime between Week 4-5 post treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05996523.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.

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