Safety run-in of intramuscular pNGVL4a-Sig/E7(detox)/HSP70 and TA-CIN vaccination as the treatment for HPV16(+) ASCUS, ASC-H, LSIL/CIN-1 (315)

Abstract

<b>Objectives:</b> The primary endpoints are to evaluate safety and tolerability, as well as the efficacy of dual pNGVL4a-Sig/E7(detox)/HSP70 and single TA-CIN intramuscular vaccination for clearance of HPV16 cervical infection at sixth month. <b>Methods:</b> Subjects were confirmed to have LSIL/CIN1, ASC-US or ASC-H, and HPV16 infection. Adverse events were evaluated using NCI CTCAE v5.0. HPV typing was done using the HPV16 18/45 Aptima Assay (Hologic) at week 0, month 6, and month 12, with simultaneous cytological analysis. Cervical biopsies and ECC were also examined at week 0 and month 6. <b>Results:</b> Twelve patients were enrolled in the safety run-in cohort, and each received all three immunizations. One was lost to followup after week 12. There were no serious adverse events noted in any subject. A total of five adverse events were noted, all grade 1; four were considered not vaccine-related, and one was ‘unlikely related.' Five of eleven (46%) participants converted to HPV16-negative at month 6. At month 6, two participants had developed CIN2+ and received a LEEP as per standard of care. At month 12, seven of 11 (64%) participants were HPV16-negative, including all five who were HPV16-negative at month 6. <b>Conclusions:</b> Initial results from the 12-patient safety run-in indicate that the repeat pNGVL4a-Sig/E7(detox)/HSP70 DNA (prime) and TA-CIN (boost) vaccine regimen was safe and well-tolerated. Five of 11 evaluable patients cleared their HPV16 infection by month 6 and remained clear at month 12. These findings will be used in the planned randomized, double-blind placebo-controlled Phase II trial.