CP-12. PHASE 0 AND FEASIBILITY SINGLE-INSTITUTION CLINICAL TRIAL OF INTRAVENOUS TOCILIZUMAB FOR ADAMANTINOMATOUS CRANIOPHARYNGIOMA

Abstract

Abstract BACKGROUND Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. ACP lacks medical antitumor therapies. Current standard therapy with surgery and radiation is associated with poor quality of life. Clinical and preclinical data indicate that IL-6 blockade may contribute to ACP tumor control. METHODS Children aged 2–21 years with newly diagnosed or previously treated ACP with measurable disease are eligible for the Phase 0/feasibility single-institution clinical trial (NCT03970226) of intravenous (IV) tocilizumab at Children’s Hospital Colorado (Aurora, CO, USA). The phase 0 stratum is completed and involved a single IV tocilizumab dose prior to a standard-of-care surgical resection. The feasibility portion of the trial involves IV tocilizumab every two weeks for up to 13 28-day cycles. Tocilizumab is administered at the established weight-based pediatric dosage of 8 mg/kg for patients who weigh ≥30kg or 12 mg/kg for patients who weigh <30kg. RESULTS Six patients (4 female; median age—10 years, range—6-15 years; 4 who had progressive disease after radiation prior to enrollment) have been treated on the feasibility stratum. The subjects have received a median of 6 cycles (range 0.5-13 cycles). The best response to date is minor response. One dose reduction for myelosuppression has been required. One patient discontinued therapy due to anaphylaxis related to tocilizumab on the first dose. CONCLUSION Systemic delivery of tocilizumab at the established pediatric dosage is promising for treatment of ACP based on preclinical work and its demonstrated penetration into cystic and solid portions of ACP tumors. The therapy to date has been well tolerated overall. Further study is underway through a CONNECT consortium international Phase II trial (NCT05233397) to explore clinical efficacy.