Journal Article

Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma

Kejner, Alexandra E., Zaidi, Mark, Anoma, Jean-Sebastien, Lee, Byung J., O’Quinn, Elizabeth C., Kaczmar, John M., Armeson, Kent E., Philipone, Elizabeth, Horn, Shane, Jordan, Victoria C., Chera, Bhishamjit S., Hill, Elizabeth G., Graboyes, Evan M., Mehrotra, Shikhar, Woods, Tina R., Troob, Scott H., Pandruvada, Subramanya, Brisendine, Alan, Nourollah-Zadeh, Farzad, Albergotti, William G., Mills, Stephanie, Kingsley, Christina, Richardson, Mary S., Yoon, Angela J., Carvajal, Richard D., Ogretmen, Besim, Spencer, Mike, Fails, Danielle, McKee, Trevor D., Newman, Jason G., Kourtidis, Antonis

2025

Overview

There is no neoadjuvant immunotherapy for early-stage oral cancer patients. We report a single-arm, open-label, pilot clinical trial assessing the efficacy and safety of topical toll-like receptor-7 (TLR-7) agonist, imiquimod, utilized in a neoadjuvant setting in early-stage oral squamous cell carcinoma (OSCC). The primary endpoint is reduction in tumor cell counts assessed by quantitative multiplex immunofluorescence and the immune-related pathologic response. The secondary endpoint is safety. 60% of patients experienced a 50% reduction or greater in tumor cell count post-treatment (95% CI = 32% to 84%). Similarly, 60% of patients had immune-related major pathologic response (irMPR) with two complete pathologic responses, and 40% had partial response (PR) with the percent residual viable tumor ranging from 25% to 65%. An increase in functional helper and cytotoxic T-cells significantly contributed to a reduction in tumor (R=0.54 and 0.55, respectively). The treatment was well tolerated with the application site mucositis being the most common adverse event (grades 1-3), and no grade 4 life-threatening event. The median follow-up time was 17 months (95% CI = 16 months - not reached), and one-year recurrence-free survival was 93% of evaluable patients. Neoadjuvant imiquimod immunotherapy could be safe and promising regimen for early-stage oral cancer. ClinicalTrials.gov, Identifier NCT04883645.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adult / Aged / Agonists / Biopsy / Cancer therapies / Cells / Clinical outcomes / Clinical trials / Cytokeratin / Cytotoxicity / Female / Head & neck cancer / Humans / Imiquimod / Imiquimod - administration & dosage / Imiquimod - adverse effects / Imiquimod - therapeutic use / Immune response / Immunofluorescence / Immunology / Immunotherapy / Immunotherapy - methods / Lymphocytes T / Male / Middle Aged / Mouth Neoplasms - drug therapy / Mouth Neoplasms - immunology / Mouth Neoplasms - pathology / Mucositis / neoadjuvant clinical trial / Neoadjuvant Therapy / Neoplasm Staging / oral cancer / Oral carcinoma / Oral squamous cell carcinoma / Patients / Pilot Projects / Review boards / Squamous cell carcinoma / toll-like 7 receptor agonist / Toll-Like Receptor 7 - agonists / Toll-like receptors / Toxicity / Treatment Outcome / Tumors