1PD - Immunotherapy with INO-3112 (HPV16 and HPV18 plasmids + IL-12 DNA) in human papillomavirus (HPV) associated head and neck squamous cell carcinoma (H...

Date 20 November 2015
Event ESMO Symposium on Immuno-Oncology 2015
Session Poster Discussion session
Topics Cancer Immunology and Immunotherapy
Head and Neck Cancers
Presenter Zane Yang
Citation Annals of Oncology (2015) 26 (suppl_8): 1-4. 10.1093/annonc/mdv513
Authors C. Aggarwal1, R. Cohen1, M. Morrow2, J. Bauml1, G. Weinstein1, J. Boyer2, J. Lee3, D. Weiner1, Z. Yang4, M. Bagarazzi3
  • 1Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia/US
  • 2Research And Development, Inovio Pharmaceuticals, Inc., Plymouth Meeting/US
  • 3Clinical Development, Inovio Pharmaceuticals, Inc., Plymouth Meeting/US
  • 4Clinical Development, Inovio Pharmaceuticals, 19462 - Plymouth Meeting/US

Abstract

Aim

HNSCCa is frequently associated with HPV infection. Immunotherapy with plasmids encoding HPV16 and HPV18 E6/E7 antigens has been shown to generate robust immune responses in women with cervical dysplasia. We hypothesize that HPV-specific immunotherapy with INO-3112 in patients with HPV-associated HNSCCa will generate robust immunity.

Methods

This prospective Phase I/IIA trial enrolled adults with HPV-positive (assessed by p16) HNSCCa in 2 cohorts. In Cohort 1, pts receive INO-3112 pre and post-surgery. In Cohort 2, pts receive INO-3112 after completion of cisplatin based chemoradiation. INO-3112 (HPV16/18 6mg + 1mg IL-12) is delivered IM followed by electroporation with the CELLECTRA® device, every 3 weeks for 4 treatments. Pts are followed for 2 years. Primary and secondary endpoints: safety and immune responses. Exploratory endpoint: anti-tumor effect. Tumor lymphocyte infiltration is studied in tumor tissue.

Results

As of June 2015, 19 pts have been enrolled. Safety data is available for 13 pts. Cohort 1: n = 3, Cohort 2: n = 10; 12 males; median age 57.7 years; cancers at base of tongue = 6, tonsil = 6, soft palate = 1; median follow-up is 104 days. INO-3112 was well tolerated with no Grade 3 or higher AEs. The most common AEs were injection site pain (n = 11), local erythema (n = 4) and hematoma/swelling (n = 2, each). 2 subjects had Grade 3 lymphopenia at baseline without worsening during the trial. There was a Grade 2, unrelated SAE of post-surgical procedure hemorrhage. Enrollment and correlative analysis are ongoing; among evaluable samples tested to date, as compared to baseline, 4 of 5 had elevated anti HPV16 and 18 E6/E7 antibody titers. 9 of 10 exhibited increase in HPV-specific IFN-gamma ELISpot. 7 of 8 had HPV-specific CD8+ T cell activation concurrent with increased lytic proteins (granzymes and perforin). All tested pts had positive cellular immune responses in at least one test.

Conclusions

These interim results demonstrate that this DNA-based immunotherapy (INO-3112) can safely generate HPV-specific CD8 T cell immunity.

Clinical trial identification

This study (NCT02163057) is co-sponsored by Inovio and the Abramson Cancer Center at the University of Pennsylvania (5P30CA016520-39).

Disclosure

Z. Yang, M. Morrow, J. Boyer, J. Lee, D. Weiner and M. Bagarazzi: I am employee of Inovio Pharmaceuticals.