Phase 1/2 study of a WT1 peptide-dosing emulsion in pediatric patients with recurrent/refractory diffuse intrinsic pontine glioma, glioblastoma, or anaplastic astrocytoma.
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BACKGROUND: The prognosis of pediatric patients with diffuse intrinsic pontine glioma (DIPG), glioblastoma, or anaplastic astrocytomas (AAs) is dismal. This first-in-child phase 1/2 study examined the safety and efficacy of a Wilms' tumor gene 1 (WT1) peptide vaccine, along with the associations of delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) frequency/count with clinical outcomes. METHODS: Patients (<20 years) were intradermally injected with the vaccine. RESULTS: Among all patients (N = 18; median age: 8.9 years), 11, 5, and 2 had DIPG, glioblastoma, and AAs, respectively. In Phase 1 (n = 4), 3.5 mg was determined for use in Phase 2 (n = 14) because no dose-limiting toxicities occurred. In Phases 1 and 2, injection site reactions (n = 14, 77.8%) were the most common adverse events. All and DIPG patients showed the 9-month overall survival (OS) rates-the primary endpoint-of 44.4% (90% confidence interval (CI) [24.4-65.9]) and 27.3% [7.9-56.4], respectively. The vaccine was not effective statistically because the lower limit of the 90% CI for the primary efficacy endpoint in DIPG patients did not exceed its prespecified threshold-20%. Median OS was 5.4 months for DIPG. Among all patients, median OS was significantly longer (p = 0.024) for WT1-specific immune responders (9.9 months [6.0-33.4]) presenting increased CTL frequency/count and/or being positive for DTH than for nonresponders (4.9 months [2.2-16.5]). CONCLUSIONS: The vaccine was not effective statistically but was well tolerated and appeared to have induced WT1-specific immune responses, suggesting improved survival in WT1-specific immune responders among DIPG patients and warranting its further development. CLINICALTRIALS: gov Identifier: NCT02750891.