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
Authors: Kline Cassie , Schoenfeld Jonathan D , Gajjar Amar , Tinkle Christopher , Margol Ashley , Davidson Tom , Bendel Anne , Skrypek Mary , Kilburn Lindsay , Packer Roger , Reddy Alyssa T , Abdelbaki Mohamed S , Rubin Josh , Sayour Elias , Mitchell Duane , Chi Susan , Waanders Angela J , Elster Jennifer , Baxter Patricia , Crotty Erin , Cohen Kenneth , Moertel Christopher , Franson Andrea T , Whipple Nicholas S , Bansal Shikha , Jankovic Vladimir , Kaul Manika , Paccaly Anne , Zhong Bob , Schmidt Tamara , Lowy Israel , Seebach Frank , Liu Kevin , Gunasti Lauren , Morinigo Denise , Singh Shefali , Shai Anny , Phillips Joanna , Filbin Mariella , Nazarian Javad , Catalano Paul , Prados Michael , Haas-Kogan Daphne , Magnan Heather , Mueller Sabine 
Published: June 2024

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 (&lt;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.