Combining an HPV vaccine with pembrolizumab for oropharyngeal cancer treatment

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

This study is testing if combining an HPV vaccine with a cancer drug can help people with newly diagnosed HPV-positive throat cancer do better than with standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: pembrolizumab, chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05996523 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of the HPV vaccine PRGN-2009 in combination with the PD-1 inhibitor pembrolizumab for patients with newly diagnosed HPV-positive oropharyngeal squamous cell carcinoma. Participants will undergo screening, physical exams, blood tests, imaging scans, and possibly biopsies before receiving the treatments. The vaccine will be administered via injection, while pembrolizumab will be given intravenously. The goal is to determine if this combination therapy can improve outcomes compared to standard treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with newly diagnosed stage I, II, or III HPV-positive oropharyngeal squamous cell carcinoma.

Not a fit: Patients with HPV-negative oropharyngeal cancer or those with distant metastasis may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance treatment efficacy and reduce the risk of disease relapse in patients with HPV-associated oropharyngeal cancer.

How similar studies have performed: Previous studies have shown promising results with similar immunotherapy approaches, indicating potential for success in this trial.

Eligibility criteria

* INCLUSION CRITERIA:
* 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.
* Ability of participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

* 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.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Charalampos Floudas, M.D. — National Cancer Institute (NCI)
• Study coordinator: Marissa B Mallek, R.N.

Conditions Oropharyngeal Squamous Cell Carcinoma; HPV16/18; PD-1 inhibitor; Monoclonal Antibody