Combination Bevacizumab and PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis (RRP)

Background: Recurrent respiratory papillomatosis (RRP) is a rare disease that causes wart-like growths called papillomas to grow in the airway, most often in the voice box, windpipe, or lungs. These growths can make it hard to speak or breathe. Surgery can remove the papillomas, but they often come back. In some cases, they can become cancerous. Objective: This study istesting whether two treatments used together (PRGN-2012, a vaccine-based treatment and bevacizumab, a drug that affects blood vessel growth) can help control RRP and reduce the chance that papillomas will grow back. Eligibility: Adults aged 18 years and older may be able to join the study if they have RRP and meet certain treatment history requirements. This may include people who have previously received PRGN-2012 or bevacizumab, or people who have needed more than 2 surgeries to remove papillomas. Design: Before starting treatment, participants will have screening tests to make sure the study is safe for them. These tests may include a physical exam with blood and urine tests, heart function testing, imaging scans, and an endoscopy. During an endoscopy, a thin, flexible tube with a small camera will look at the inside of the nose, throat, voice box, and upper windpipe. Participants will receive study treatment during 7 clinic visits over about 6 months. Bevacizumab is given through a vein amd PRGEN-2012 is given as an injection under the skin of the arm or leg. Participants may receive 1 or both drugs at each visit. After completing treatmen, participants will return for 4 follow-up visits over 1 year. These visits may include repeat imaging, blood and urine tests, and other exams. After that, the study team will contact participantsby phone or email every 3 months for 2 years. If their RRP gets worse during the follow-up period, they may be able to receive a second course of treatment using the same schedule....

* INCLUSION CRITERIA: * Histological or cytological diagnosis of RRP confirmed by pathology report. Note: If there is no documentation or archival sample, a biopsy will be done to confirm the diagnosis. * Age \>= 18 years old. * A history of 2 or more surgeries or use of IV bevacizumab in order to control laryngeal and/or tracheal RRP within 12 months prior to the study treatment initiation. * Previous treatment with PRGN-2012 (zopapogene imadenovec \[Papzimeos\]). * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Participants must have an adequate organ and marrow function as defined below: * White blood cells (WBC) \>2,000/mcL * Absolute neutrophil count (ANC) \>= 1,000/mcL * Hemoglobin \> 9.0 g/dL * Platelets \>= 100,000/mcL * Total bilirubin \150 mmHg and/or diastolic blood pressure \> 100 mmHg). Note: an average of 3 BP readings on 2 sessions will be used to measure blood pressure if the initial reading indicates inadequately controlled hypertension. Anti-hypertensive therapy to achieve blood pressures below these parameters is allowed. * Prior history of hypertensive crisis or hypertensive encephalopathy. * Persisting toxicity related to prior therapy of Grade \>1 per CTCAE. Note: Alopecia, sensory neuropathy Grade \= Grade 3 per CTCAE infusion-related reaction to bevacizumab or PRGN-2012. * Pregnancy confirmed with beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test in WOCBP at screening. * Uncontrolled symptomatic, intercurrent illness evaluated by medical history, physical exam, and labs, or social situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study, or that would limit compliance with study requirements.