A Perioperative Study of Safusidenib in Patients with IDH1-Mutated Glioma

10 participants with a radiological or pathological diagnosis of WHO Grade 2 lower-grade glioma (LGG) were recruited at a single center starting in December, 2022. Eligibility criteria permitted participants who had undergone prior surgery for WHO Grade 2 LGG, but excluded those with a history of prior radiation or chemotherapy.In Part A of the study, participants underwent an initial craniotomy with tumor biopsy and a lumbar puncture for cerebrospinal fluid (CSF) collection at study entry. Following sample collection, participants received safusidenib at the recommended phase 2 doses of 250 mg twice daily (b.i.d.) for a period of 22–36 days. This was followed by a second craniotomy for maximal safe tumor resection and a repeat lumbar puncture within 5 hours of the final pre-resection dose of safusidenib. Tumor, blood, and CSF samples were collected at both surgical time points for comprehensive translational research.Molecular analyses were performed on samples collected at both time points. These included pharmacokinetics (PK), targeted metabolomics, whole-genome sequencing (WGS) of tumor tissue, single-nucleus RNA sequencing (snRNA-seq), and DNA methylation profiling on all patients. Targeted metabolomics was conducted on samples from 9 participants, while spatial transcriptomics and spatial metabolomics were performed on tumor tissue from 3 participants each. Histone methylation profiling was conducted on samples from 8 participants.]]>
Patients with a MRI diagnosis (including MR spectroscopy and perfusion imaging sequences) consistent with adult low-grade glioma (aLGG) who require surgical resection were screened for this study. In addition, patients with known IDH1 mutated aLGG requiring further surgical resection who had previously only undergone surgery were also screened. Patients with contrast enhancement, or other features of high-grade glioma were excluded.Inclusion criteria included adults aged ≥18 years with a radiological or pathological diagnosis of aLGG who do not require urgent resection for mass effect or hydrocephalus according to the treating neurosurgeon. Patients who required urgent resection, had received chemotherapy or radiation therapy or had a cerebellar or brainstem tumor were excluded from the study.Additional eligibility criteria included adequate hepatic and renal function, ECOG performance status score 0 or 1, and a lesion evaluable by LGG-RANO criteria.]]>