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About
This phase II trial tests how well pB1-11 and human papillomavirus tumor antigen (TA-HPV) vaccines in combination with pembrolizumab work in treating patients with oropharyngeal cancer that has come back (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic) and that is PD-L1 and human papillomavirus (HPV) positive. Oropharyngeal cancer is a type of head and neck cancer involving structures in the back of the throat (the oropharynx), such as the non-bony back roof of the mouth (soft palate), sides and back wall of the throat, tonsils, and back third of the tongue. Scientists have found that some strains or types of a virus called HPV can cause oropharyngeal cancer. pBI-11 is a circular deoxyribonucleic acid (DNA) (plasmid) vaccine that promotes antibody, cytotoxic T cell, and protective immune responses. TA-HPV is an investigational recombinant vaccina virus derived from a strain of the vaccina virus which was widely used for smallpox vaccination. Vaccination with this TA-HPV vaccine may stimulate the immune system to mount a cytotoxic T cell response against tumor cells positive for HPV, resulting in decreased tumor growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread by inhibiting the PD-1 receptor. These investigational vaccines could cause or enhance an immune response in the body against HPV, during which time the activity of pembrolizumab against oropharyngeal cancer associated with HPV may be strengthened. These drugs in combination may be more effective in increasing the ability of the immune system to fight oropharyngeal cancer than pembrolizumab alone.
Full description
PRIMARY OBJECTIVE:
I. To assess the safety and feasibility of intramuscular PVX7 (pBI-11/pBI-11/human papillomavirus tumor antigen vaccine [TA-HPV]) immunization in patients with HPV+ recurrent/metastatic (R/M) oropharyngeal carcinoma (OPC) undergoing treatment with pembrolizumab.
SECONDARY OBJECTIVE:
I. To assess the response rate (RR) of the addition of pBI-11 and TA-HPV to pembrolizumab (P) as first line therapy for patients with PD-L1+ (combined positive score [CPS] >= 1), HPV+, R/M OPC.
EXPLORATORY OBJECTIVES:
I. To evaluate the overall survival (OS), progression free survival (PFS) and safety of the combination of PVX7 and pembrolizumab in this population.
II. To evaluate correlates of clinical activity by: (1) comparing HPV16/18 E6/E7-specific cellular and humoral immunity in pre- versus (vs.) post-pBI-11 and TA HPV-treated OPC patients that are pembrolizumab responders (R) and/or non-responders (NR).
OUTLINE:
Patients receive pBI-11 vaccine intramuscularly (IM), TA-HPV vaccine IM, and pembrolizumab intravenously (IV) on study. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection during screening and on study. Patients may undergo tumor biopsy during screening and on study.
Enrollment
Sex
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Volunteers
Inclusion criteria
Exclusion criteria
Disease that can be treated with curative intent as assessed by patient's study physician. If patient in this situation wishes for treatment with palliative intent then they may enroll
Multiple primary oropharyngeal (OP) tumors
Primary cancer not originated from the oropharynx
Has received any therapy for R/M disease. Therapy in the setting of curative intent is allowed
Patient is pregnant or breastfeeding
Prior prophylactic or therapeutic vaccination with any human papillomavirus (HPV) antigen except L1
* Note: previous receipt of the Gardasil (registered trademark) vaccine (including Gardasil 9 [registered trademark]) or the Cervarix (registered trademark) vaccine does not exclude
Has received a live vaccine within 30 days prior to first dose of study treatment
Is currently participating in or, within 4 weeks prior to first dose of study treatment, has participated in a study of an investigational agent or has used an investigational device
Diagnosis of immunodeficiency
Known additional malignancy that is non-localized or progressing or has required active treatment within the past 3 years prior to first dose of study treatment
* Note: Participants with usual basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (for example, in situ cervical cancer or breast carcinoma, superficial bladder cancer, or non-invasive intraductal carcinoma of the prostate) that have undergone potentially curative therapy are not excluded
Radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator and radiology review
Recipient of previous allogeneic tissue/solid organ transplant
Known severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
History of myocarditis or pericarditis or other known clinically significant underlying heart disease (e.g., cardiomyopathy, congestive heart failure, symptomatic arrhythmia not controlled by medication, unstable angina, history of acute myocardial infarction)
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, sepsis, or psychiatric illness/social situations that would limit compliance with study requirements
Active or chronic infection with any of the following (with testing for all three conditions required during screening for this study):
Active autoimmune disease with immunodeficiency as a clinical component (e.g., rheumatoid arthritis, systemic lupus erythematosus [SLE], ulcerative colitis, Crohn's disease, multiple sclerosis [MS], ankylosing spondylitis)
Within 60 days prior to initiating first dose of protocol-indicated treatment, patient has received therapy with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), alkylating agents, antimetabolites, radiation, tumor necrosis factor (TNF) inhibitors, or systemic corticosteroids
Recognized immunodeficiency diseases including cellular immunodeficiencies; hypo-gammaglobulinemia or dys-gammaglobulinemia; or acquired, hereditary, or congenital immunodeficiencies
Patients and their close social, sexual, or domestic contacts may not have non-healed wounds or active exfoliative skin conditions, such as eczema, burns, impetigo, varicella-zoster virus infection, herpes simplex virus infection, severe acne, severe diaper dermatitis with extensive areas of denuded skin, psoriasis, lichen planus, or Darier disease (keratosis follicularis)
History and presence of atopic dermatitis
Patients and their close social, sexual, or domestic contacts may not have known conditions associated with immunosuppression, such as HIV/acquired immunodeficiency syndrome (AIDS), leukemia, lymphoma, generalized malignancy, solid organ transplant recipient, or hematopoietic stem cell transplant recipient < 24 months post-transplant OR >= 24 months, but who have graft-versus-host disease or disease relapse, or be of less than 1 year of age
Found at screening visit to have severe arrhythmias (e.g., atrial fibrillations), sinus bradycardia (< 50 beats per minute [BPM]), sinus tachycardia (> 100 BPM) via resting electrocardiography (EKG). Patients with controlled arrhythmias followed by a cardiologist are eligible
Patients with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids. Hypoxemia (oxygen saturation [SpO2] < 92% for 5 min or longer) by finger pulse oximetry corrected by oxygen supplementation is allowed
Primary purpose
Allocation
Interventional model
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54 participants in 1 patient group
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Vanderbilt-Ingram Services for Timely Access
Data sourced from clinicaltrials.gov
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