Abstract
BACKGROUND
Brain tumors are the leading cause of pediatric cancer-related death.
METHODS
We report interim outcome data from an ongoing multi-site phase 2 study (NCT04049669) of indoximod-based chemo-immunotherapy for patients 3-21 years of age with either recurrent brain cancer (ependymoma, medulloblastoma, high-grade glioma) or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Treatment is oral IDO pathway-inhibitor indoximod (38.4 mg/kg/day, divided BID) plus temozolomide (200 mg/m2/day for 5 days) in 28-day cycles. Patients who may benefit from additional irradiation receive indoximod during the radiation regimen and are analyzed separately.
RESULTS
Planned accrual is 140; 80 patients have been treated to date. Estimated median follow-up time was 23.5 months (range 0.2 - 42.7 months), and indoximod-based therapy has been well tolerated. Estimated median overall survival (OS) was 23.8 months for recurrent ependymoma (n=31); 11.5 months for recurrent medulloblastoma (n=22); 5.7 months for recurrent HGG (n=18, includes diffuse midline glioma except primary DIPG); and 15.0 months for newly diagnosed DIPG (n=9). Single-cell TCR and RNA sequencing of serially collected blood samples was used to identify expanded CD8+ T cell clones with late-effector phenotypes, and their emergence was associated with significantly improved survival. In patients treated with immunotherapy, radiographic measurement of objective response is challenging, owing to the high incidence of mixed responses and pseudoprogression events. In our recently published phase 1 trial of indoximod (NCT02502708, Neuro-Oncology 26:348-361, 2024) we showed that 41% of relapsed patients had MRI evidence of objective response in at least one tumor using RAPNO criteria, and that these “responder” patients had 3-fold better median OS (25.2 months, p=0.007) than non-responders (7.3 months). To date, the phase 2 data is similar.
CONCLUSIONS
The GCC1949 phase 2 study is replicating the published phase 1 results, and we will present updated results from the first 80 patients in the GCC1949 trial.