LBA-01. Tumor and systemic molecular / immune correlates and patient reported QOL in pediatric CNS and solid tumors treated with PD1 inhibition and conventional versus hypofractionated radiation on PNOC013

Background We investigated PD-1 inhibition (cemiplimab) as monotherapy in recurrent solid and central nervous system (CNS) tumors (phase 1) and in combination with standard or hypofractionated radiation therapy (RT) followed by cemiplimab monotherapy in children, adolescents, and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) or recurrent HGG (phase 2). Methods PNOC013 was a multicenter study conducted through the Pediatric Neuro-Oncology Consortium (PNOC). Correlative analyses included: 1) biologic correlates - tumor molecular profiles, intra-tumoral PD-1 pathway components and immune infiltration and circulating cytokines and 2) clinical correlates – imaging, quality-of-life (QoL), and hypofractionated and standard RT plans. Results Fifty-seven patients were treated across all cohorts. >90% of tumors did not express PD-L1 as measured by immunohistochemistry. Overall low/undetectable levels of CD3+ T cells, CD20+ B cells, CD68+ myeloid cells were found. CD4+ T cells were prominent when T cells were present. Thirty-three (58%) underwent cytokine analysis (n = 99 samples) with cytokine patterns differing by patient. IL-8 (p = 0.01), IL-17a (p = 0.06), IP-10 (p = 0.09), MIP-1a (p = 0.05) tended to increase between baseline and end of therapy (EOT), while other cytokines remained stable. QoL batteries (n = 38 parents, n = 33 patients) trended towards worse cognitive problems, pain and hurt, and worry based on parent report and stability per patient report. RT plans demonstrated mostly minor deviations with major deviations related to undercoverage of target volume due to dose contraints. Conclusions PNOC013 provides biologic and clinical insight for pediatric patients with newly diagnosed and recurrent DIPG, HGG, and recurrent malignant solid or CNS tumors, including the: immunologically cold environment of these tumors; potential promise of combinatorial therapy strategies such as PD-1 and IL-8 blockade; challenges to longitudinally collect QOL in high-grade tumors; and, feasibility to combine conventionally fractionated RT, hypofractionated RT, and reRT with PD-1 inhibition. Integrated molecular analyses for this cohort continue.