What question did this study set out to answer?

To evaluate the safety and preliminary efficacy of pembrolizumab in children with recurrent high-grade gliomas and hypermutant tumors.

March 14, 2026Open Access

IMMU-05. Outcome of patients with hypermutant or recurrent high-grade gliomas treated with pembrolizumab, an immune checkpoint inhibitor: a Pediatric Brain Tumor Consortium study (PBTC045).

Key Points

To evaluate the safety and preliminary efficacy of pembrolizumab in children with recurrent high-grade gliomas and hypermutant tumors.
Participants with recurrent high-grade gliomas or hypermutant tumors were enrolled according to specific eligibility criteria.
Pembrolizumab was administered at 2 mg/kg IV every three weeks for up to 34 courses.
Correlative studies involved the collection of tumor tissue and serum samples.
23.3% of treated patients had anaplastic astrocytoma.
Grade 3 adverse events included hematologic, neurologic, general, and pseudoprogression, with no severe drug-attributed adverse events.
1-year progression-free survival rates were 21.4% for Stratum B and 54.5% for Stratum C, with durable objective responses in both.

Abstract

Abstract Background Children with recurrent high-grade gliomas (HGGs) and hypermutant brain tumors have dismal prognoses but may respond to immune checkpoint blockade. PBTC045 is a safety/preliminary efficacy study of pembrolizumab, a PD-1 inhibitor. Here we present the strata that included recurrent HGG and upfront or progressive hypermutant tumors. Methods Eligible patients had recurrent/progressive HGG (Stratum B) or hypermutant tumors (Stratum C, newly diagnosed or recurrent) with functional scores 70, no greater than physiologic steroid usage and without bulky disease, among other standard eligibility criteria. Pembrolizumab was administered at 2mg/kg IV every three weeks; maximum treatment duration was 34 courses. Tumor tissue and serum were collected for correlative studies. Primary endpoints included toxicity and objective response (OR) rate, with a two-stage design requiring durable OR (partial response or better sustained at least 9 weeks) for expansion. Results Eligible patients were enrolled for Strata B, C (recurrent or newly diagnosed): n = 14, n = 5, and n = 11, respectively. Median age at enrollment was 13.5 yrs. (4.8-19.9), 14.1 yrs. (4.6-25.3), and 16.2yrs (range,12.4-25.3), respectively, and were 60% male overall. Seven patients (23.3%) had anaplastic astrocytoma. No drug-attributed grade 4-5 adverse events (AEs) occurred. Grade 3 AEs included hematologic (n = 6), neurologic (n = 4), general (n = 2), and pseudoprogression (n = 1). Two patients in Stratum B (14.3%) and two in Stratum C (n = 2, 18.2%) had sustained ORs. Several patients completed the full course of therapy. The 1-year PFS was 21.4% (95% CI, 5.2-44.8%), 0%, and 54.5% (95% CI, 22.9%-78%), respectively. The study did not complete full accrual. Conclusions As a single agent, pembrolizumab treatment is well tolerated. Notably, in our study, there were durable responses in both newly diagnosed hypermutant and recurrent HGG, suggesting that response is not solely predicated on mutational status. Immune correlate work is ongoing.

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