Ssim 02-07IMMUNOTHERAPY WITH INO-3112 (HPV16 AND HPV18 PLASMIDS + IL-12 DNA) IN HUMAN PAPILLOMAVIRUS (HPV) ASSOCIATED HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCCA)

22. HPV and oropharynx / Head and neck cancer
C. Aggarwal 1, R. Cohen 1, M. Morrow 2, K. Kraynyak 2, J. Bauml 1, G. Weinstein 1, J. Boyer 2, J. Yan 2, D. Mangrolia 2, S. Oyola 2, J. Lee 2, S. Duff 2, Z. Yang 2, M. Bagarrazi 2.
1University of Pennsylvania (United States), 2Inovio Pharmaceuticals (United States)

Background / Objectives

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.


Methods

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.


Results

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.

 


Conclusion

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.

 

 


References

This study (NCT02163057) is co-sponsored by the Abramson Cancer Center at the University of Pennsylvania and Inovio Pharmaceuticals.