Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer
Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer
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.
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.
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:
Design:
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 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:
Adequate renal and hepatic function at screening, as follows:
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.
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-human chorionic gonadotropin (hCG) at screening
Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with the exception of:
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.