Brain Cancer — Glioblastoma (GBM) Clinical Trials

About Brain Cancer — Glioblastoma (GBM) trials

GBM trials are stratified by molecular profile because the WHO 2021 brain tumor classification reclassified glioblastoma along molecular lines: only IDH-wildtype tumors are now formally called GBM, while IDH-mutant tumors are classified as IDH-mutant astrocytoma grade 4. IDH1 and IDH2 are tested at diagnosis and define which tumor classification (and therefore which trial set) applies. MGMT promoter methylation status is the most important treatment-predictive biomarker for GBM, predicting response to temozolomide chemoradiation and gating many trial designs. TERT promoter mutations are present in roughly 80% of IDH-wildtype GBM and contribute to molecular classification. EGFR amplification, including the EGFRvIII variant, defines a target for some trials. PTEN, CDKN2A, and TP53 are common alterations that contribute to molecular subtype and trial stratification. BRAF mutations (especially V600E) are rare in adult GBM but actionable, and matter more in pediatric and young adult astrocytomas. H3F3A (rendered as H3 K27M in the chip) defines diffuse midline glioma, a separate disease that has its own trial set, more common in pediatric and young adult patients than in older adults. HER2 (ERBB2) testing is emerging for trials of HER2-targeted ADCs.

Recruiting trials cluster by classification, treatment line, and molecular target. Newly diagnosed IDH-wildtype GBM trials test additions to or modifications of the Stupp protocol (chemoradiation with temozolomide followed by adjuvant temozolomide), often stratified by MGMT methylation status. Recurrent GBM trials are an active and crowded space because effective treatment options at recurrence are limited, with novel mechanisms, immunotherapy, oncolytic viruses, and tumor-treating fields (TTFields) combinations all in trial. IDH-mutant astrocytoma trials are a separate set, particularly with IDH-targeted approvals expanding into earlier lines and grade-2 / grade-3 disease. Diffuse midline glioma (H3 K27M) trials are typically separate, often pediatric or young adult focused, and test imipridone-class agents and other H3 K27M-targeted approaches. BRAF V600E trials test targeted combinations in the rare adult cases. EGFR-amplified trials test ADCs, vaccines, and CAR-T approaches. Vaccine and oncolytic virus trials remain a major area despite mixed phase 3 outcomes historically.

Common eligibility filters in GBM trials include classification, MGMT status, and clinical fitness. Tumor classification confirmation: most trials are specific to IDH-wildtype GBM, IDH-mutant astrocytoma, or diffuse midline glioma. MGMT promoter methylation status is required for many newly diagnosed trials and used for stratification in others. Karnofsky Performance Status (KPS): most trials require ≥60 or ≥70. Steroid dose: many immunotherapy and vaccine trials cap dexamethasone at low doses (e.g., ≤4 mg/day), so steroid taper before screening is often required. Time since last radiation matters for recurrence trials (typically requiring at least 12 weeks since RT to distinguish true progression from pseudoprogression). Prior bevacizumab exposure is a defining criterion for many recurrence trials, with separate cohorts for bev-naïve and bev-pretreated. Tumor measurability by RANO criteria is required for response assessment. Surgical accessibility for tissue-required or resection-followed-by-treatment trials. Age criteria vary, with adult trials typically 18+ and some trials open to younger adults or pediatric patients.

Biomarkers tested in Brain Cancer — Glioblastoma (GBM) trials

These are the molecular markers most commonly required or evaluated in Brain Cancer — Glioblastoma (GBM) eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.