Phase II Trial of Anti-PD1 Therapy for HPV-associated Recurrent Respiratory Papillomatosis (IND#128874)

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PROJECT ABSTRACT Recurrent Respiratory Papillomatosis (RPP) is an orphan disease with approximately 20,000 active cases in the United States and with an incidence of approximately 4.3 per 100,000 children and 1.8 per 100,000 adults. RRP is caused by infection with human papillomavirus (HPV) types 6 and 11 and is characterized by mucosal tumors that grow in the respiratory tract, impacting breathing, swallowing, and speech. In 3-5% of patients, the lesions can undergo malignant transformation and the prognosis for patients who develop cancers derived from their RRP is poor. There is no effective systemic therapy for RRP, despite the fact that it typically involves multiple sites. Thus, there is a strong unmet need to develop novel treatment options for RRP patients. We and others have shown that RPP is a disease characterized by an ineffective host immune response to HPV, in part, through the upregulation of the PD1:PDL1 axis. Thus, we hypothesize that administration of a blocking PD-1 monoclonal antibody, pembrolizumab, can re-activate host anti-tumor responses, leading to the regression of existing RPP lesions, clearance of chronic HPV infection, and prevention of new disease as a means to improve the quality of life and achieve possible cure. To test this hypothesis, we have opened an investigator-initiated phase II clinical trial administering pembrolizumab to subjects diagnosed with advanced RPP to evaluate the effectiveness of immunotherapy as a novel treatment option. In this study, biopsies and peripheral blood samples are obtained every 12 weeks while receiving study treatment, which provides a unique longitudinal sampling of tissue to understand how the tumor, tumor immune microenvironment, and host immune responses may evolve over time. We seek support to perform key correlative analyses of the pre- and on-treatment human samples to generate essential data, investigating the role of immunotherapy as a novel and effective treatment option for RRP patients.