Dr Johnson on Immune Activation With Indoximod-Based Chemo-Immunotherapy in Recurrent Ependymoma

“[We] found that over half the patients had immune activation with clonal expansion of T cells [and] that those T cells tended to be highly activated with upregulation of pathways related to killing target cells.”

Theodore S. Johnson, MD, PhD, co-director of the Pediatric Immunotherapy Program and a professor of pediatric oncology at Augusta University and the Wellstar Health System, discussed interim outcome and pharmacodynamic data from a phase 2 trial (NCT04049669) evaluating the oral IDO pathway inhibitor indoximod plus temozolomide (Temodar) in patients with recurrent ependymoma, data from which were presented at the 2026 SNO Annual Meeting (SNO 2026).

Blocking IDO has been shown to break tolerance to apoptotic tumor cells when combined with chemotherapy, Johnson explained. This SNO presentation focused on the subgroup of patients with ependymoma (n = 54), he said. Adding indoximod to moderate-intensity oral temozolomide led to responses in some patients, which may be related to prolonged survival in those patients, according to Johnson. The estimated median overall survival (OS) in the 54 patients was 23.8 months.

The investigators combined single-cell T-cell receptor sequencing with single-cell RNA sequencing to measure immune responses in patients’ blood, developing a clonal expansion index that adds all expanded T-cell clones in a sample and normalizes them to the sample’s total T cells, Johnson explained. Comparing on-treatment samples with those collected at baseline, more than half of patients showed immune activation with clonal expansion of T cells, and these T cells were highly activated, with upregulation of pathways related to killing target cells, Johnson noted.

With the trial running for many years, survival data are available for several patients, Johnson said. In the 51-patient training set of patients with various tumor histologies, which was separated by high vs low clonal expansion index, the median OS was 26.3 months in the high-CEI group (n = 29) vs 7.6 months in the low-CEI group (n = 22; P < .002).

That finding prompted subgroup analyses, Johnson said. In the 15 sequenced patients with ependymoma, those with high immune activity again had significantly prolonged OS vs those with poor immune responses. The respective median OS values were 23.8 months (n = 10) vs 13.0 months (n = 5; P = .012).