TRLS-03. A PHASE 1/2 STUDY ASSESSING SAFETY AND PHARMACOKINETICS OF CEMIPLIMAB IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY SOLID OR CENTRAL-NERVOUS-SYSTEM TUMORS AND SAFETY AND EFFICACY OF CEMIPLIMAB IN COMBINATION WITH RADIOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA, NEWLY DIAGNOSED HIGH-GRADE GLIOMA, OR RECURRENT HIGH-GRADE GLIOMA

Abstract

Abstract BACKGROUND We investigated, for the first time, combination PD-1 inhibition (cemiplimab) and radiation therapy (RT) followed by cemiplimab monotherapy in children with solid tumors, diffuse intrinsic pontine glioma (DIPG) and high-grade glioma (HGG). METHODS We conducted a multicenter study through the Pediatric Neuro-Oncology Consortium. Phase 1 established the safety/pharmacokinetics of cemiplimab monotherapy in children (<18 years) with recurrent solid and central-nervous-system (CNS) tumors. Phase 2 evaluated cemiplimab/RT in children and young adults (3-25 years) with newly diagnosed (nd) DIPG, ndHGG or recurrent HGG (rHGG). Patients with ndDIPG and ndHGG were randomized to hypofractionated RT (hfRT) or conventionally fractionated RT (cRT). Primary endpoints included overall survival at 12 months (OS12) for ndDIPG and rHGG and progression-free survival at 12 months (PFS12) for ndHGG. Correlates included quality-of-life, circulating tumor DNA (ctDNA), immunogenicity, and PD-1 pathway components. RESULTS 25 patients (solid tumors, n=8; CNS tumors, n=17) were treated in phase 1; serum drug concentrations were comparable to adults. 32 patients were treated in phase 2. OS12 was 33.3% for ndDIPG treated with cemiplimab/hfRT (n=6), 0.0% for ndDIPG with cemiplimab/cRT (n=5), and 31.3% for rHGG (n=9). PFS12 was not estimable for ndHGG treated with cemiplimab/hfRT (n=5) and 20.0% for ndHGG treated with cemiplimab/cRT (n=7). 20 patients (35.1%) had grade 3/4 treatment-related AEs (TRAEs) and 13 (22.8%) had serious TRAEs. The most frequent grade 3/4 TRAE was decreased lymphocyte count (n=4 [7.0%]). 12 patients (21.1%) demonstrated treatment-emergent pseudo-progression, 2 (3.5%) grade 3/4. The most frequent serious TRAE was pseudo-progression (n=3 [5.3%]). CONCLUSIONS Cemiplimab/RT did not demonstrate an improvement in OS (ndDIPG and rHGG) or PFS (ndHGG), leading to early stopping for futility. However, the combination was tolerable, demonstrated similar outcomes across RT schedules, and showed similar exposure in serum compared to adults. Biologic and clinical correlate analyses are underway.