Oropharyngeal HNSCCa is frequently associated with HPV infection. DNA-based immunotherapy with plasmids encoding HPV16 and HPV18 E6/E7 antigens has been shown to generate robust immune responses in women with HPV-driven high-grade cervical dysplasia. We hypothesize that immunotherapy with INO-3112 in patients (pts) with HPV-associated HNSCCa will generate robust immunity contributing to disease control.
This open-label Phase I/IIa trial included adults with HPV-positive HNSCCa. Cohort 1, pts received INO-3112 pre and post-surgery; Cohort 2, pts received INO-3112 after completion of cisplatin based chemoradiation. INO-3112 was delivered intramuscularly followed by electroporation with the CELLECTRA® device, every 3 weeks for 4 doses. Pts are followed for 2 years. Primary and secondary endpoints are safety and immune responses. Exploratory endpoint: clinical response.
As of January 2016, 20 pts have been treated. Cohort 1: n=6, Cohort 2: n=14; 18 males, median age 57 years; cancers at base of tongue=7, tonsil=13; never smoker=8; median follow-up of 195 days. INO-3112 was well tolerated, with no treatment related Grade 3 AE, no ≥ Grade 4 AEs. The common (≥10%) AEs were injection site pain (n=14), injection site erythema (n=4), injection site swelling (n=3), dizziness (n=3), dysphagia (n=2), injection site hematoma (n=2) and candidiasis (n=2). Two unrelated SAEs: Grade 2 post-surgical procedure hemorrhage and Grade 3 acute non-traumatic kidney injury. Enrollment and correlative analysis are ongoing. Among samples tested to date (n=10), as compared to baseline, all 10 evaluable pts showed elevated antigen specific antibody titers. Nine of 10 evaluable pts exhibited increased HPV-specific cellular responses by IFN-gamma ELISpot. Eight out of 9 evaluable pts had HPV-specific CD8+ T cell responses to INO-3112 by flow cytometric analysis and all 10 pts had positive cellular immune responses in at least one assay.
These interim data demonstrate that INO-3112 can be administered safely in pts with HPV-related HNSCCa. All evaluable pts demonstrated humoral and cellular immune response, including generation of HPV-specific CD8+ T cells.
This study (NCT02163057) is co-sponsored by the Abramson Cancer Center at the University of Pennsylvania and Inovio Pharmaceuticals.