A Randomized Double-Blind Placebo-Controlled Phase I/II Clinical Trial of a Human Papillomavirus Therapeutic Vaccine, PepCan, for Reducing Head and Neck Cancer Recurrence.

OBJECTIVES

Head and neck cancer (HNC) has a high recurrence rate. Safety and effectiveness of PepCan in reducing recurrence for HNC patients were assessed.

METHODS AND ANALYSIS: PepCan consists of four human papillomavirus 16 (HPV 16) E6 peptides and a Candida skin testing reagent (Candin®, Nielsen Biosciences) as a vaccine adjuvant. Since Candida was known to have a general immune stimulating effects, patients were recruited regardless of their HPV status. Men and women with HNC who had no evidence of disease after standard surgery, chemotherapy, and/or radiation treatments were enrolled. They were randomized at 3:1 to PepCan versus placebo. Seven intradermal injections of PepCan or placebo (saline) were given every 3 weeks (first 4 injections) or 3 months (last 3 injections). They were followed with two visits 6 months apart. Safety was assessed using Common Terminology Criteria for Adverse Events version 5, and efficacy was assessed based on not having recurrence within 2 years. In addition, immune responses were examined using enzyme-linked immunospot assay for HPV 16 E6 response, fluorescent-activated cell sorter analysis for peripheral immune cells, and T cell repertoire analysis. Peripheral cytokines and gut and oral microbiome were also analyzed.

RESULTS

Seventeen patients were enrolled. The most common adverse events were grades 1 and 2 injection site reactions, and they occurred more frequently in the PepCan group (p<0.0001). Two patients had allergic reactions (grade 2 and grade 3), at the 6th vaccination, which were considered to be a dose-limiting toxicity (DLT). No serious adverse events were reported. In the intention-to-treat analysis (ITT), 45% (5/11) had non-recurrence in the PepCan group while 80% (4/5) had non-recurrence in the placebo group. For the per-protocol (PP) analysis, non-recurrence was 56% (5/9) for PepCan and 80% (4/5) for placebo. These differences were not statistically significant. Those who received PepCan and experienced non-recurrence had higher new T cell immune responses to HPV 16 E6 (p=0.05 for ITT and p=0.02 for PP). Pre-vaccination T helper type 1 cells were higher in the PepCan non-recurrence group compared to the PepCan recurrence group (p=0.01 for ITT and PP).

CONCLUSIONS

PepCan is safe although DLT can occur after multiple injections of PepCan. PepCan does not seem to be effective in reducing recurrence; however, the results are inconclusive given the small patient numbers.

TRIAL REGISTRATION NUMBER: NCT03821272.