Abstract 4104: Randomized phase II trial of imiquimod with or without 9vHPV vs observation in patients with CIN 2 and 3

Abstract Introduction: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator, vs imiquimod plus a 9-valent human papillomavirus vaccine (9vHPV) vs surveillance in cervical intraepithelial neoplasia (CIN) 2 and 3 patients. Methods: We randomly allocated 133 patients with untreated CIN 2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (arm B) or imiquimod plus 9vHPV (arm C) vs clinical surveillance (arm A). The main outcome was efficacy, defined as histologic regression to CIN 1 or less. Secondary outcomes were HPV clearance and treatment tolerability. Exploratory objectives included the comparison of cervical CD4/CD8 T-cell infiltration at baseline, mid-study, and post-treatment by flow-cytometry. Results: Of the 114 evaluable patients 77% and 23% had CIN2 and CIN3, respectively. Histologic regression to CIN1 or less was observed in 95% of patients in the Arm B: imiquimod group and 84% in the Arm C: imiquimod+9vHPV compared with 79% in Arm A: surveillance (p=0.043 and 0.384, respectively). The difference between either treatment arm compared with control did not reach the prespecified α=0.025. No significant differences were noted in HPV clearance. The number of tissue-resident memory CD4/CD8 T-cells in cytobrush samples demonstrated a >5-fold increase in Arm-B: imiquimod when compared to Arm-A: surveillance (p<0.01). Imiquimod treatment was well tolerated. In contrast, there was no significant difference in T-cell responses among participants in Arm-C compared to Arm-A. Imiquimod treatment was well-tolerated. Conclusions: Although imiquimod induced a higher percentage of regression to CIN1 or less and significant increases in CD4/CD8 T-cells infiltrating the cervix, it did not meet its prespecified statistical outcome for efficacy. A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trial with imiquimod targeting CIN3 patients are warranted. Citation Format: Sangini S. Sheth, Ji Eun Oh, Stefania Bellone, Eric R. Siegel, Natalia Buza, Akiko Iwasaki, Alessandro D. Santin. Randomized phase II trial of imiquimod with or without 9vHPV vs observation in patients with CIN 2 and 3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4104.