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Immunotherapy with VGX-3100 (HPV16 and HPV18 plasmids) + INO-9012 (DNA encoding IL-12) in human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCCa): interim safety and immunogenicity results

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Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P426

https://doi.org/10.1186/2051-1426-3-S2-P426

  • Published:

Keywords

  • Cervical Dysplasia
  • Injection Site Pain
  • Robust Immune Response
  • Adequate Organ Function
  • Exploratory Endpoint

Background

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 HPV-specific immunotherapy with INO-3112 (VGX-3100 + INO-9012) in patients with HPV-associated HNSCCa will generate robust immunity which may contribute to disease stabilization or regression.

Method

Eligibility for this prospective Phase I/IIa trial included adults with HPV-positive (assessed by p16) HNSCCa, ECOG PS 0-1, and adequate organ function. Patients (pts) are enrolled into two 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 (6mg of VGX-3100 plus 1mg of INO-9012) is delivered IM followed by electroporation with the CELLECTRA® device, once every 3 weeks for a total of 4 doses. Pts are followed for 2 years. Primary and secondary endpoints are safety and immune responses. Exploratory endpoints include: anti-tumor effect and progression-free-survival. Assessment of post-immunotherapy surgical specimens is being done to evaluate vaccine-induced lymphocyte infiltration in tumor.

Results

As of June 2015, 19 pts have been enrolled. Complete safety data is available for 13 pts. Cohort 1: n=3, Cohort 2: n=10; 12 males; median age 57.7 years (range 39-76); cancers at base of tongue=6, tonsil=6, soft palate=1; never smoker=5, 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). Two subjects had Grade 3 lymphopenia at baseline and no worsening during the trial. There was a Grade 2, unrelated SAE of post-surgical procedure hemorrhage. Enrollment and correlative analysis are ongoing; among samples tested to date, as compared to baseline, 4 of 5 evaluable pts showed elevated anti HPV16 and 18 E6/E7 antibody titers. Nine of 10 evaluable pts exhibited increased HPV-specific cellular responses by IFN-gamma ELISpot. Seven of 8 evaluable pts had HPV-specific CD8+ T cell activation concurrent with increased lytic proteins (granzymes and perforin) by flow cytometric analysis.

Conclusion

These interim results demonstrate that this DNA-based immunotherapy (INO-3112) can safely generate HPV-specific CD8 T cell immunity in patients with HPV-related HNSSCa. All tested pts had positive cellular immune responses in at least one assay.

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

Trial Registration

ClinicalTrials.gov identifier NCT02163057.

Authors’ Affiliations

(1)
University of Pennsylvania, Philadelphia, PA, USA
(2)
Inovio Pharmaceuticals, Plymouth Meeting, PA, USA
(3)
Inovio Pharmaceuticals, San Diego, CA, USA
(4)
Inovio, Philadelphia, PA, USA
(5)
Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA, USA

Copyright

© Aggarwal et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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