PepCan therapeutic vaccine fails to significantly reduce HNSCC recurrence in small phase I/II trial

Recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) after standard-of-care treatments remains a significant challenge, often leading to poor prognosis. Current therapies struggle to prevent recurrence effectively, highlighting an unmet need for adjunctive strategies. Therapeutic vaccines, particularly those targeting human papillomavirus (HPV)-associated HNSCC, offer a promising approach by stimulating the patient's immune system to recognize and eliminate residual cancer cells. PepCan, an HPV16 E6 peptide-based vaccine, was developed to address this gap by inducing specific anti-tumor immune responses.

This randomized, double-blind, placebo-controlled phase I/II clinical trial enrolled 17 patients with head and neck squamous cell carcinoma (HNSCC) who had no evidence of disease after standard-of-care treatments. Patients were randomized 3:1 to receive PepCan (four HPV16 E6 peptides + Candida skin testing reagent) versus placebo (saline). Participants received seven intradermal injections, followed by two observational visits. Safety was assessed using CTCAE version 5, and efficacy was determined by the absence of recurrence within 2 years. Immune responses and oral/gut microbiome were also evaluated.

Seventeen patients were enrolled in the study. The most common adverse events were grades 1 and 2 injection site reactions, occurring more frequently in the PepCan group (p < 0.0001). Two patients experienced allergic reactions (grade 2 and grade 3) at the 6th vaccination, identified as a dose-limiting toxicity. No serious adverse events were reported. In intention-to-treat analyses, efficacy for recurrence reduction was not observed:

45% (5/11) of patients in the PepCan group achieved non-recurrence, compared to 80% (4/5) in the placebo group (p = not significant). However, patients receiving PepCan who did not recur showed a trend of higher new peripheral T cell immune responses to human papillomavirus type 16 E6 (p = 0.05). Furthermore, pre-vaccination T helper type 1 cells were significantly higher in the PepCan non-recurrence group compared to the PepCan recurrence group (p = 0.01), suggesting a potential biomarker for response.