GBM Clinical Trial Landscape Analysis

What this research found

Glioblastoma (GBM) attracts a large volume of trial activity that has produced very few approvals. All 1,913 interventional GBM trials registered on ClinicalTrials.gov were retrieved, classified by therapeutic modality and molecular target, and compared against the five drugs and one device approved for the disease. The widest gap is immunotherapy: 682 trials, 35.7% of the landscape, against no approved immunotherapy agent for GBM.

• Immunotherapy is the field's largest bet with no return so far — 682 trials (35.7%) against zero approved agents — with checkpoint inhibitors aimed at PD-1, PD-L1, and CTLA-4 making up much of that group.
• Novel targets rarely reach pivotal trials. Phase 3 to early-phase ratios were 0.074 for MET (26 against 353 trials), 0.053 for PD-1 (6 against 114), 0.046 for EGFR (3 against 65), and 0.018 for mTOR (1 against 55). Only MGMT cleared 0.1, at 0.180.
• A quarter of the pipeline retreads approved ground: 495 trials (25.9%) use mechanism classes that are already approved, with alkylating agents appearing in 642 trials and angiogenesis inhibitors in 194, while 397 trials (20.8%) pursue novel mechanisms.
• Academic groups run the field but hand off late-stage work. Academic and other non-commercial sponsors lead 1,301 trials (68.0%) against industry's 468 (24.5%), yet industry sponsors 46 of the Phase 3 trials (40.0%). Federal sponsors account for 7.5% of all trials and 3.5% of Phase 3.
• The landscape is mature but attrition-heavy: 904 trials are completed and 247 were terminated. A keyword scan of 198 recent papers found negative-outcome language co-occurring with all five leading targets, from a ratio of 0.50 for MET to 0.64 for EGFR.

How it was done

Interventional trials were pulled from the ClinicalTrials.gov API for the query Glioblastoma OR Glioblastoma Multiforme, yielding 1,913 records. A rule-based classifier assigned each to modalities — device or procedure, small molecule, immunotherapy, viral or gene therapy — and tagged molecular targets and drug classes, and a baseline of five approved agents, one approved device, and four key biomarkers was assembled for comparison. Gap analysis then measured overlap with standard of care, per-target phase progression ratios, and negative-sentiment co-occurrence across 198 PubMed papers from 2021 to 2026, while sponsors were split into academic, industry, and federal using the registry's sponsor class field. The output was a 21-page report with seven figures and a companion blog post of about 1,100 words.

Data sources

• ClinicalTrials.gov API v2 — 1,913 interventional glioblastoma trials
• PubMed via NCBI E-utilities — 198 articles on GBM trials, standard of care, and failures (2021–2026)
• Approved-therapy baseline — temozolomide, bevacizumab, lomustine, carmustine, carmustine wafer, and tumour treating fields

Figures from this analysis

Outputs produced

• raw_trials.json

  Raw clinical trial data for Glioblastoma (1913 interventional trials)

• raw_literature.json

  PubMed literature on GBM clinical trials, standard of care, and failures (198 articles)

• approved_therapies.json

  Approved GBM therapies baseline for Gap Analysis (5 agents + TTFields device)

• processed_trials.json

  Processed trials with modality and MoA classifications

• trials_flat.csv

  Flattened trial data for analysis (4449 intervention rows)

• gap_analysis.json

  Quantitative gap analysis metrics (SoC overlap, novel targets, phase attrition, literature sentiment)

• gap_analysis_summary.md

  Human-readable gap analysis summary with 3 key gaps and recommendations

• final_synthesis.json

  Aggregated findings from all analysis steps for writing agent