Abstract 68: Phase I Study of Self-Administered Artesunate Pessaries for Treatment of Cervical Precancer in HIV- Positive and HIV-Negative Women in Kenya

Abstract Purpose: Cervical cancer disproportionately affects women in in low- and middle-income countries, where it accounts for 85% of cases and 90% of deaths globally. Although WHO’s 90/70/90 cervical cancer elimination strategy aims to treat 90% of cervical precancers by 2030, treatment access remains limited. In Kenya, only 5% of hospitals provide precancer treatment, and just 30% of women in 2022 received it. Innovative methods, such as self-administered topical therapies, could help bridge this treatment gap. Artesunate, derived from the antimalarial artemisinin, has shown promise against HPV in lab studies. In a Phase I U.S. trial, self-administered intravaginal artesunate led to 63% disease regression of cervical intraepithelial neoplasia grade 2/3 (CIN2/3), and a Phase II is underway. We are conducting a Phase I trial in Kenya (NCT06165614) to evaluate its feasibility as CIN2/3 therapy. Methods: Eighteen women with CIN2/3 will self-administer intravaginal artesunate for 5 days on weeks 1, 3, 5, and 7. The primary objective is safety; secondary outcomes include adherence, histologic regression (CIN1 or lower), and acceptability. Treatment response is evaluated by colposcopy and biopsy at week 14. Those with persistent CIN2/3 undergo excision, while those with regression to CIN1 or less will be monitored. The trial began in March 2024. Results: Seventeen women (mean age of 39.9 years) are enrolled; 15 (88.2%) are HIV-positive and on antiretroviral therapy, with a mean CD4 count of 627.8 cells/mm3. Most participants (58.8%) are married and have at least a primary education (64.7%). All reported at least one grade 1 adverse event (AE), commonly vaginal discharge (60%) and headache (53.3%). Six grade 2 AEs (perineal or pelvic pain, headache) were reported, with no grade 3 or 4 AEs. Adherence, assessed by self-report and returned pessary covers, was excellent. Of 15 participants completing week 14 colposcopy visits, 11 (73.3%) had persistent CIN2/3 or worse and underwent excision or hysterectomy, while 4 (26.6%) regressed to CIN1 or less and are under observation. Study visits continue, with samples stored for HPV genotyping and microbiome testing. Conclusion: Early U.S. studies of intravaginal artesunate showed potential efficacy for CIN2/3. However, preliminary results from our ongoing Phase I study in Kenyan women, most of whom are living with HIV, suggest lower response rates. Further analyses will explore the impact of HPV genotype and microbiome. Citation Format: Chemtai Mungo, Cirilus Ogollah, Gershon Rota, Kate Sorgi, Elizabeth Bukusi, Jennifer H. Tang, Lisa Rahangdale, Jackton Omoto. Phase I Study of Self-Administered Artesunate Pessaries for Treatment of Cervical Precancer in HIV- Positive and HIV-Negative Women in Kenya [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 68.