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Background Recurrent respiratory papillomatosis (RRP) is a rare disease caused by chronic infection with human papillomavirus (HPV) types 6 or 11. Viral oncoproteins E6 and E7 increase expression of vascular endothelial growth factor (VEGF) which promotes angiogenesis and accumulation of regulatory T cells and myeloid derived suppressor cells in tumors. 1 2 Therapeutic inhibition of VEGF can decrease infiltration of immune suppressive cells, promoting trafficking of cytotoxic CD8+ T cells.3 Despite these immunologic features, current RRP treatment consists of repeated interventions to debulk or ablate tumors rather than medical therapies that address the underlying infection. We present clinical findings from our ongoing trial of bevacizumab-bvzr in adult patients with RRP.Methods In the single-arm, phase 2 study, patients receive bevacizumab-bvzr 10 mg/kg IV every 3 weeks for 3 cycles then every 6 weeks for 8 cycles ( NCT05797246). Patients require ≥2 interventions in the 12 months prior to treatment plus one of the following: Derkay score (a measure of papilloma burden) of ≥8, tracheal or pulmonary RRP. Primary objective is to determine percentage of patients with an increase in intervention-free interval comparing the 12 months pre-treatment to 12 months on treatment. Secondary objectives include safety and objective response rate of pulmonary tumors. Exploratory objectives include measurement of peripheral and papilloma-infiltrating HPV-specific T cells.Results As of June 5th, 2025, 19 patients have completed the 1-year treatment course. Patients had severe baseline disease indicated by a median of 2 (range, 2-4) interventions in the 12 months prior to treatment, median Derkay score of 12 (range, 1-30) and median vocal handicap index (VHI)-10 score of 26 (range, 6-38). Adverse events occurring in ≥20% of patients included grade 1 or 2 headache, hypertension, fatigue, arthralgia, dysgeusia and oral pain. Disease control and voice improvement was rapid with median Derkay score decreasing from 12 to 4 and median VHI-10 from 26 to 11 following the first dose. During treatment, 1 patient required 1 intervention to control disease, significantly lower than the 54 interventions needed in the 20 patients the year prior ( figure 1). Twelve of twelve evaluable patients experienced papilloma regrowth by the 6-month post-treatment evaluation, suggesting persistent HPV infection.Conclusions Systemic bevacizumab-bvzr demonstrated rapid and consistent clinical benefit by eliminating the need for interventions during treatment. Combination treatment with a targeted immune agent capable of inducing HPV-specific T cell responses may eliminate persistent infection and papilloma regrowth that occurs upon cessation of bevacizumab-bvzr.Trial Registration This trial was registered on clinicaltrials.gov, trial number NCT05797246.References Terme M, Pernot S, Marcheteau E, Sandoval F, Benhamouda N, Colussi O, et al. VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res. 2013 Jan 15;73(2):539–49.Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Jung S, et al. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell. 2006 Jan 13;124(1):175–89.Yang J, Yan J, Liu B. Targeting VEGF/VEGFR to MODULATE ANTITUMOR IMMUNITY. Front Immunol. 2018;9:978.Ethics Approval This study was approved by the NIH IRB; approval number IRB001572.Abstract 551 Figure 1Swimmer’s plot depicting number of interventions required in the 12 months before treatment (left) compared to the number of interventions during treatment (right) over time (x-axis) in each patient treated (y-axis). Complete response was defined as no requirement for intervention during the 12-month treatment period. Patient 17 received 2 doses of bevacizumab-bvzr before developing a grade 3 infusion related reaction following dose 2 and was subsequently removed from protocol therapy