Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma
BackgroundThere 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...
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Frontiers Media S.A.
2025-01-01
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| author | Angela J. Yoon Richard D. Carvajal Evan M. Graboyes John M. Kaczmar William G. Albergotti Alexandra E. Kejner Scott H. Troob Elizabeth Philipone Jean-Sebastien Anoma Kent E. Armeson Elizabeth G. Hill Mary S. Richardson Tina R. Woods Bhishamjit S. Chera Farzad Nourollah-Zadeh Byung J. Lee Subramanya Pandruvada Antonis Kourtidis Christina Kingsley Elizabeth C. O’Quinn Stephanie Mills Victoria C. Jordan Mike Spencer Danielle Fails Trevor D. McKee Mark Zaidi Alan Brisendine Shane Horn Shikhar Mehrotra Besim Ogretmen Jason G. Newman |
| author_facet | Angela J. Yoon Richard D. Carvajal Evan M. Graboyes John M. Kaczmar William G. Albergotti Alexandra E. Kejner Scott H. Troob Elizabeth Philipone Jean-Sebastien Anoma Kent E. Armeson Elizabeth G. Hill Mary S. Richardson Tina R. Woods Bhishamjit S. Chera Farzad Nourollah-Zadeh Byung J. Lee Subramanya Pandruvada Antonis Kourtidis Christina Kingsley Elizabeth C. O’Quinn Stephanie Mills Victoria C. Jordan Mike Spencer Danielle Fails Trevor D. McKee Mark Zaidi Alan Brisendine Shane Horn Shikhar Mehrotra Besim Ogretmen Jason G. Newman |
| author_sort | Angela J. Yoon |
| collection | DOAJ |
| description | BackgroundThere 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).MethodsThe primary endpoint is reduction in tumor cell counts assessed by quantitative multiplex immunofluorescence and the immune-related pathologic response. The secondary endpoint is safety.Results60% 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.ConclusionNeoadjuvant imiquimod immunotherapy could be safe and promising regimen for early-stage oral cancer.Trial registrationClinicalTrials.gov, Identifier NCT04883645. |
| format | Article |
| id | doaj-art-ff507d34458e4b91a3f3c787ddcead8e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-ff507d34458e4b91a3f3c787ddcead8e2025-01-27T06:40:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15302621530262Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinomaAngela J. Yoon0Richard D. Carvajal1Evan M. Graboyes2John M. Kaczmar3William G. Albergotti4Alexandra E. Kejner5Scott H. Troob6Elizabeth Philipone7Jean-Sebastien Anoma8Kent E. Armeson9Elizabeth G. Hill10Mary S. Richardson11Tina R. Woods12Bhishamjit S. Chera13Farzad Nourollah-Zadeh14Byung J. Lee15Subramanya Pandruvada16Antonis Kourtidis17Christina Kingsley18Elizabeth C. O’Quinn19Stephanie Mills20Victoria C. Jordan21Mike Spencer22Danielle Fails23Trevor D. McKee24Mark Zaidi25Alan Brisendine26Shane Horn27Shikhar Mehrotra28Besim Ogretmen29Jason G. Newman30Medical University of South Carolina, Charleston, SC, United StatesNorthwell Health Cancer Institute, New Hyde Park, NY, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesColumbia University Irving Medical Center, New York, NY, United StatesColumbia University Irving Medical Center, New York, NY, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesFortis Life Sciences, Montgomery, TX, United StatesFortis Life Sciences, Montgomery, TX, United StatesPathomics, Toronto, ON, CanadaPathomics, Toronto, ON, CanadaMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesMedical University of South Carolina, Charleston, SC, United StatesBackgroundThere 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).MethodsThe primary endpoint is reduction in tumor cell counts assessed by quantitative multiplex immunofluorescence and the immune-related pathologic response. The secondary endpoint is safety.Results60% 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.ConclusionNeoadjuvant imiquimod immunotherapy could be safe and promising regimen for early-stage oral cancer.Trial registrationClinicalTrials.gov, Identifier NCT04883645.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1530262/fulloral cancerneoadjuvant clinical trialtoll-like 7 receptor agonistimiquimodimmunotherapy |
| spellingShingle | Angela J. Yoon Richard D. Carvajal Evan M. Graboyes John M. Kaczmar William G. Albergotti Alexandra E. Kejner Scott H. Troob Elizabeth Philipone Jean-Sebastien Anoma Kent E. Armeson Elizabeth G. Hill Mary S. Richardson Tina R. Woods Bhishamjit S. Chera Farzad Nourollah-Zadeh Byung J. Lee Subramanya Pandruvada Antonis Kourtidis Christina Kingsley Elizabeth C. O’Quinn Stephanie Mills Victoria C. Jordan Mike Spencer Danielle Fails Trevor D. McKee Mark Zaidi Alan Brisendine Shane Horn Shikhar Mehrotra Besim Ogretmen Jason G. Newman Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma Frontiers in Immunology oral cancer neoadjuvant clinical trial toll-like 7 receptor agonist imiquimod immunotherapy |
| title | Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma |
| title_full | Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma |
| title_fullStr | Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma |
| title_full_unstemmed | Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma |
| title_short | Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma |
| title_sort | pilot clinical trial of neoadjuvant toll like receptor 7 agonist imiquimod immunotherapy in early stage oral squamous cell carcinoma |
| topic | oral cancer neoadjuvant clinical trial toll-like 7 receptor agonist imiquimod immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1530262/full |
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