DNA immunotherapy for recurrent respiratory papillomatosis (RRP): phase 1/2 study assessing efficacy, safety, and immunogenicity of INO-3107

Matthew P. Morrow (), Elisabeth Gillespie, Albert Sylvester, Milan R. Amin, Peter C. Belafsky, Simon R. Best, Aaron D. Friedman, Adam M. Klein, David G. Lott, Ted Mau, Randal C. Paniello, Seth M. Pransky, Nabil F. Saba, Grace S. Tan, Sadie Wisotsky, Sarah A. Marcus, Emma L. Reuschel, Katherine S. Reed, David B. Weiner, Michael Dallas and Jeffrey M. Skolnik
Additional contact information
Matthew P. Morrow: Inovio Pharmaceuticals
Elisabeth Gillespie: Inovio Pharmaceuticals
Albert Sylvester: Inovio Pharmaceuticals
Milan R. Amin: New York
Peter C. Belafsky: University of California
Simon R. Best: Johns Hopkins University School of Medicine
Aaron D. Friedman: University of Cincinnati Medical Center
Adam M. Klein: Emory University
David G. Lott: Mayo Clinic Arizona
Ted Mau: University of Texas Southwestern Medical Center
Randal C. Paniello: Washington University School of Medicine
Seth M. Pransky: Pediatric Specialty Partners
Nabil F. Saba: Emory University
Grace S. Tan: Inovio Pharmaceuticals
Sadie Wisotsky: Inovio Pharmaceuticals
Sarah A. Marcus: Inovio Pharmaceuticals
Emma L. Reuschel: Inovio Pharmaceuticals
Katherine S. Reed: Inovio Pharmaceuticals
David B. Weiner: The Wistar Institute
Michael Dallas: Inovio Pharmaceuticals
Jeffrey M. Skolnik: Inovio Pharmaceuticals

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity Score (modified) post-INO-3107 and assessment of immune responses. 81% (26/32) of patients experienced surgery reduction following INO-3107 compared with the year prior to treatment. Blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction. RNA sequencing identified an inflammatory response in papillomas, inclusive of cytolytic CD8 + T-cell signatures. T-cell receptor sequencing revealed emergent T-cell clones in blood and confirmed trafficking to papillomas. Treatment-related adverse events (AEs) were reported in 13/32 (41%) patients, all low-grade. INO-3107 provides clinical benefit to HPV-6 and/or HPV-11-associated RRP adults and is well-tolerated. Importantly, treatment-induced peripheral T-cell responses traffic to airway tissue and are associated with clinical response.

Date: 2025
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DOI: 10.1038/s41467-025-56729-6

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