UAZ22-10-01: A Phase IIa single-arm open-label clinical trial of calcipotriene plus 5-fluorouracil immunotherapy for skin cancer prevention in organ transplant recipients

Summary: Abstract Body: Squamous cell carcinoma (SCC) significantly increases morbidity and mortality in organ transplant recipients (OTRs); however, effective SCC prevention strategies for OTRs are lacking. In immunocompetent patients, we demonstrated that topical calcipotriene plus 5-fluorouracil (5-FU) induced thymic stromal lymphopoietin and antigen presentation, promoting the induction of CD4+ T helper 2 (Th2) immunity and tissue-resident memory T (TRM) cell formation in actinic keratoses (AKs) leading to AK clearance. Th2-derived cytokines induced interleukin (IL)-24 in malignant keratinocytes, resulting in cytotoxic autophagy and anoikis, a mechanism distinct from CD8+ T cell cytotoxicity potentially harmful for transplanted organs. To assess the activity and safety of calcipotriene plus 5-FU immunotherapy for OTRs, an open-label multi-site Phase IIa trial (NCT05699603) has been initiated. The trial will enroll 56 kidney or lung transplant recipients with 4-15 AKs in 25 cm2 on the upper/lower extremities, chest, face, and/or scalp with repeated biopsy of AKs and normal skin. Treatment involves one or two courses of topical calcipotriene plus 5-FU given twice daily for six days to evaluate T cell immunity and AK clearance. The primary endpoint is CD4+ TRM cell induction in AKs one day after completing one or two courses of treatment. Secondary endpoints include evaluating TRM cell persistence at 6 months, AK clearance across anatomical sites, and safety. Enrollment began in August 2024 and is ongoing. Marjan Azin¹, Tomonori Oka¹, Chiu-Hsieh P. Hsu², Joshua Malo⁷, Kassem Safa⁶, Clara N. Curiel-Lewandrowski⁵, Milan J. Anadkat⁴, Rajan P. Kulkarni³, Margaret House⁸, Julie E. Bauman⁹, Patricia Thompson², Malgorzata Wojtowicz⁸, Shadmehr Demehri¹ 1. Massachusetts General Hospital, Boston, MA, United States. 2. The University of Arizona, Tucson, AZ, United States. 3. Oregon Health & Science University, Portland, OR, United States. 4. Washington University in St Louis, St. Louis, MO, United States. 5. The University of Arizona, Tucson, AZ, United States. 6. Massachusetts General Hospital, Boston, MA, United States. 7. The University of Arizona, Tucson, AZ, United States. 8. National Cancer Institute Division of Cancer Prevention, Bethesda, MD, United States. 9. The George Washington University, Washington, DC, United States. Clinical Research: Interventional Research