e18038 Background: Approximately 10-15% of patients with HPV16+ HNSCC develop recurrent, incurable disease after definitive therapy. NavDx is a tumor tissue-modified viral (TTMV) HPV DNA assay that can detect minimal residual disease (MRD) in peripheral blood prior to clinical or radiographic recurrence, with a positive predictive value of approximately 95%. MRD represents a novel clinical setting in patients with HPV16+ HNSCC and allows identification of a high-risk subset of patients for early intervention. HB-200 is an arenavirus-based therapeutic vaccine, consisting of alternating HB-202 and HB-201, designed to elicit a T-cell response against the HPV16 E6 and E7 oncoproteins. We conducted a pilot study to evaluate the feasibility of treating patients with MRD-positive HPV16+ HNSCC using HB-200. Methods: Patients with histologically proven HPV16+ HNSCC who completed definitive therapy without evidence of clinical or radiographic disease, but with detectable NavDx, were enrolled. Patients received 2 cycles of HB-200 (42-day Cycle: HB-202 1x10⁷ RCV FFU on D1, HB-201 5x10⁶ RCV FFU on D22). Peripheral blood for NavDx and E6/E7 ELISPOT was collected at pre-, on-, and post-treatment time points. Imaging was performed pre-treatment and after two cycles of HB-200. The primary endpoint was feasibility, as defined by identification and enrollment of patients with HNSCC HPV16+ MRD and completion of HB-200 treatment. Secondary endpoints included safety, NavDx kinetics, and disease-free survival (DFS). Results: Five patients were enrolled. See Table 1 for clinical annotation and NavDx time points. Patient #2 discontinued early due to pathologic confirmation of recurrent disease after 1 cycle. Patients #1 and #5 remain disease free (NED) by imaging and exam after treatment. Patient #1 remained NavDx-negative and NED for >12 months. Median DFS for the cohort was 110 days (23-455). All patients had detectable increases in E6/E7-specific antigen T-cells by ELISPOT; 4/5 patients had a >8-fold increase in E6 and 3/5 patients had a >8-fold increase in E7 antigen specific T-cells after one cycle of HB-200. These levels declined but persisted at 2-3 fold above baseline after treatment completion. All patients completed therapy with no grade > 3 adverse events. Conclusions: HB-200 therapy can clear TTMV-HPV DNA detected by NavDx in a subset of patients with HPV16+ HNSCC MRD and induces E6/E7 antigen specific T-cells. Treatment of MRD is feasible and further study is warranted to establish the therapeutic standard. Clinical trial information: NCT06373380. Patient #1 Patient #2 Patient #3 Patient #4 Patient #5 Age/Sex 68 y/o M 67 y/o M 59 y/o M 60 y/o M 67 y/o M Baseline NavDx 70 4 35 4 4 On Treatment NavDx 5 NA 35 Negative Indeterminate End of Treatment NavDx Negative NA 185 6 4 Current Status NED NED after 3 cycles of anti-PD1 monotherapy Active disease receiving chemotherapy + anti-PD1 Active disease receiving chemo-radiation NED
Wong et al. (2026) studied this question.