IMMU-04. Multi-antigen T cell Infusion Against Neuro-oncologic Disease (ReMIND): A phase I clinical trial

Central nervous system (CNS) tumors are the most common, and deadliest, solid cancers in children, and novel therapies are urgently needed. We hypothesize that polyclonal multi-tumor-associated-antigen T-cell therapy (TAA-T) may benefit patients with high-risk brain tumors where intratumoral heterogeneity plays a prominent role in therapeutic resistance. Pediatric patients with high-risk CNS tumors were enrolled on a phase I dose escalation study (NCT03652545) to determine the safety and feasibility of autologous TAA-T expanded ex vivo using dendritic cells pulsed with peptide libraries spanning the antigens WT1, PRAME, and Survivin. Patients were enrolled at three dose levels in three strata: newly-diagnosed diffuse intrinsic pontine glioma (DIPG, Arm A, n = 11) and recurrent/progressive non-brainstem CNS malignancies without (Arm B, n = 18) or with (Arm C, n = 4) lymphodepletive conditioning (dose level 3 only). Arms B/C included high-grade glioma (n = 16), medulloblastoma (n = 9), ependymoma (n = 7), astroblastoma (n = 1), and pineoblastoma (n = 1). Infusions were generally well tolerated; however, two patients with high tumor burden experienced possibly-related serious adverse events (grade 5 for Arm A; grade 3 for Arm B). Dose level 3 (8x107 cells/m2) was established as the maximum tolerated dose. In Arm A, median overall survival was 12.9 months. In Arm B, one patient with glioblastoma exhibited prolonged post-­infusion survival of five years, two patients (medulloblastoma and glioblastoma) show no evidence of disease more than two years after TAA-T treatment, and one patient with medulloblastoma continues to exhibit prolonged disease stability more than three years post-infusion. In Arm C, one patient with H3K27M-­altered and TP53-altered spinal high-grade glioma, lived 27.3 months post-­infusion, and one patient with astroblastoma achieved a radiographic complete response and remains alive more than two years post-infusion without recurrence. TAA-T cells show some preliminary signals of efficacy and warrant further evaluation in patients with high-risk, non-brainstem CNS malignancies following tumor resection and adjuvant therapy.