A peptide-based human papillomavirus therapeutic vaccine, PepCan, or Candida adjuvant alone in treatment of cervical intraepithelial neoplasia 2/3 (CIN2/3)

5538 Background: A non-surgical alternative for treating CIN2/3 would be desirable for women of childbearing age due to a risk of cervical incompetency in subsequent pregnancies following surgical treatments. PepCan consists of four current good manufacturing-grade HPV 16 E6 peptides and a Candida skin testing reagent (Candin, Nielsen Biosciences), because of Candida’s ability to regress common warts in humans, and to promote T cell proliferation and interleukin-12 secretion in vitro. Methods: In this single-center, randomized, double-blind Phase II study (NCT02481414), women with biopsy-confirmed CIN2/3 were treated with PepCan or Candida (1:1). Four intradermal injections were given 3 weeks apart which were followed with two visits 6 months apart. Histological responses (primary endpoint) were assessed using quadrant biopsies, and those whose lesions regressed to no CIN were considered to be responders. Regression rate of each treatment group was compared to that of a historical placebo group following the same treatment schedule. A sample size of 35 per arm had 93% power to test the null hypothesis that π = 0.29 (historical control placebo rate) and detect a difference of 0.31 with a two-sided type I error of 5%. Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events Version 4. Results: Of 99 subjects screened, 81 (81.8%) qualified for vaccination, and 80 received at least one vaccination. No dose-limiting toxicity was observed. With the intention-to-treat analysis, PepCan showed 30.8% efficacy (12 of 39, p=0.16) while Candida demonstrated 47.6% efficacy (20 of 42, p=0.0004). Likewise, with the per-protocol analysis, PepCan showed 45.8% efficacy (11 of 24, p=0.06) and Candida showed 62.1% efficacy (18 of 29, p=0.0002). There was no difference between efficacy of PepCan and Candida. Conclusions: PepCan and Candida treatments are safe. Only Candida was effective in inducing histological regression in the intention-to-treat and per-protocol analyses. Candida could become a new treatment for CIN2/3 by eliciting general immune stimulation similar to checkpoint inhibitors. Clinical trial information: NCT02481414 . [Table: see text]