Work

525 Open-label study of zopapogene imadenovec-drba retreatment and vector shedding evaluation in adult patients with recurrent respiratory papillomatosis

Year: 2026

Type: conference-abstract

Abstract: Background Recurrent respiratory papillomatosis (RRP) is a rare, neoplastic disorder caused by chronic infection with human papillomavirus (HPV) type 6 or 11. Repeat surgical debulking has been the most common treatment for RRP. Zopapogene imadenovec-drba (zopa), a novel adenovector-based immunotherapy, is the first and only FDA-approved treatment for adults with RRP. In the pivotal study, robust efficacy was observed following zopa treatment with 51% (34 to 69; 95% CI) of patients achieving a complete response (CR). 83% (15/18) of patients that achieved a CR at 12 months (m) remained in CR after a duration of follow-up of at least 36m (range: 36-51m). Zopa was well-tolerated with no serious adverse events and no grade >2 treatment-related adverse events. Neutralizing antibody (NAb) titers collected up to 52-weeks post-treatment remained at low to undetectable levels and there was no correlation between NAb titer and clinical response. Zopa is recommended as first-line treatment for adults with RRP in an RRP Foundation position statement.1 One cohort of the following ongoing study will evaluate the presence of vector shedding in adults with RRP who had no prior zopa treatment. Another cohort aims to determine whether retreatment with zopa can eliminate the need for subsequent papilloma debulking procedures in adults with RRP.Methods This trial ( NCT06538480) is an open-label, multi-center, study enrolling patients in two cohorts. The primary endpoint of the first cohort will evaluate the magnitude and duration of zopa vector shedding for up to 6 weeks in 10 patients with no prior exposure to zopa. Another cohort will evaluate the safety and efficacy of zopa in 20 patients with RRP, who have previously received zopa treatment. The primary endpoint of the retreatment cohort is the rate of CR, defined as the percentage of patients with no requirement for surgery in the 12m following treatment completion. Key endpoints include time to the first post-treatment debulking procedure after retreatment completion, vocal function change, extent of papilloma growth, and induction of HPV-specific T cell responses. Patients must be ≥18 years old with a clinical diagnosis of RRP irrespective of the number of prior surgeries, satisfactory organ function, ECOG 0-1, and the presence of laryngotracheal papillomas. Exclusion criteria: active autoimmune disease, steroid use >10mg prednisolone-equivalent daily, pregnancy or uncontrolled illness.Trial Registration ClinicalTrials.gov ID: NCT06538480Reference Best SR, Friedman AD, Rosen CA, et al. Recurrent respiratory papillomatosis foundation position statement on the management of adults With RRP. Laryngoscope 2026;0:1–11. doi:10.1002/lary.70379.Ethics Approval The study obtained ethics approval from the NIH Intramural IRB, 6700B Rockledge Drive, Ste. 4300 Bethesda,Maryland USA 20817. The number/ID of the approval(s) are as follows: IRB ID: IRB001969 / IRB001969 The study obtained ethics approval from Advarra 6100 Merriweather Drive, Suite 600Columbia, Maryland 21044, USA IRB#00000971/MOD02837177 IRB#00000971/MOD02763185 IRB#00000971/CR00636834 IRB#00000971 /MOD02191744 IRB#00000971/MOD02517909 IRB#000 00971/MOD02653567 IRB#00000971/MOD02631779 IRB# 00000971/SSU00293687 IRB#00000971/MOD02489988 IRB# 00000971/MOD02363890 IRB#00000971/SSU00253735 IRB#00000971/MOD02281981 IRB#00000971/ MOD0227 0072 IRB#00000971/ MOD02167219 IRB#00000971/ MOD0 2168813 IRB#00000971/ MOD02134004 All study participants gave informed consent before taking part and were reconsented according to the NIH IRB and Advarra guidelines.

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-sitc2026.0525