TPS9595 Background: Basal cell carcinoma (BCC) is the most common human cancer. Although laBCC and mBCC are rare (<10,000 cases per year in the US), tumors are typically locally invasive and often destroy skin and surrounding structures, leading to substantial morbidity. Standard-of-care therapies include hedgehog pathway inhibitors (HhPi) (e.g., vismodegib, sonidegib), but these medications may be poorly tolerated due to side effects (e.g., muscle spasms, alopecia, dysgeusia), and anti-tumor responses often lack durability. Several published reports have described patients with advanced HhPi-refractory BCC who experienced durable, objective tumor regressions after administration of anti-PD-1, which may be better tolerated than HhPi. The purpose of this study is to evaluate the efficacy of NIVO (anti-PD-1) alone and in combination with IPI (anti-CTLA-4) in patients with laBCC or mBCC, either in the first-line setting or after HhPi therapy. Methods: NCT03521830 is an open-label, phase 2 study of NIVO alone (cohort A) and plus IPI (cohort B) for patients with laBCC or mBCC. Subjects enrolled to cohort A (treatment-naïve or after HhPi therapy) will receive NIVO 480mg IV q4 weeks for up to 48 weeks. Subjects with progressive BCC after anti-PD-1 +/- HhPi will enroll to cohort B and receive NIVO 240mg + IPI 1mg/kg IV q3 weeks x 4 doses followed by NIVO 480mg IV q4 weeks x 7 doses. The primary endpoint is objective response rate (ORR) per RECIST v1.1. Secondary endpoints are duration of response, progression-free and overall survival, and disease control rate (i.e., % of patients with stable disease lasting ≥26 weeks or complete or partial response). Exploratory studies will include assessment of changes in immune cell subsets and immune checkpoint expression in pre- and on-treatment tumor biopsies, correlated with clinical outcomes. A Simon’s two stage design is planned for each cohort, testing for 15% null vs. 40% alternative ORR for cohort A, and 5% null vs. 20% alternative ORR for cohort B. The study will enroll up to 19 patients on cohort A and 21 patients on cohort B. Subject accrual began in November 2018. Clinical trial information: NCT03521830.
988 An open-label phase 2 clinical trial of topical remetinostat gel for basal cell carcinoma
