{ "metadata": { "analysis_date": "2026-01-22T18:46:31.434064", "analysis_type": "Gap Analysis", "data_sources": { "trials": "1913 trials from ClinicalTrials.gov", "approved_therapies": "5 approved agents", "literature": "198 PubMed articles" } }, "soc_overlap_analysis": { "total_trials": 1913, "approved_mechanism_trials": 495, "novel_mechanism_trials": 397, "mixed_trials": 284, "unclassified_trials": 737, "by_modality": { "Small Molecule": { "total": 1002, "approved": 773, "novel": 430 }, "Device/Procedure": { "total": 1132, "approved": 501, "novel": 393 }, "Immunotherapy": { "total": 682, "approved": 359, "novel": 295 }, "Other": { "total": 310, "approved": 22, "novel": 73 }, "Viral/Gene Therapy": { "total": 97, "approved": 22, "novel": 27 } }, "by_target": { "VEGF": { "total": 200, "is_approved": true }, "IDH": { "total": 37, "is_approved": false }, "MET": { "total": 363, "is_approved": false }, "PD-1": { "total": 100, "is_approved": false }, "MGMT": { "total": 63, "is_approved": false }, "mTOR": { "total": 42, "is_approved": false }, "ALK": { "total": 19, "is_approved": false }, "EGFR": { "total": 61, "is_approved": false }, "CDK": { "total": 17, "is_approved": false }, "CTLA-4": { "total": 20, "is_approved": false }, "TERT": { "total": 8, "is_approved": false }, "BRAF": { "total": 7, "is_approved": false }, "PARP": { "total": 23, "is_approved": false }, "PD-L1": { "total": 25, "is_approved": false }, "MEK": { "total": 7, "is_approved": false }, "PI3K": { "total": 6, "is_approved": false } }, "by_class": { "Alkylating agent": { "total": 642, "is_approved": true }, "Angiogenesis inhibitor": { "total": 194, "is_approved": true }, "Kinase inhibitor": { "total": 159, "is_approved": false }, "Cell cycle inhibitor": { "total": 23, "is_approved": false }, "Epigenetic modifier": { "total": 9, "is_approved": false }, "Checkpoint inhibitor": { "total": 34, "is_approved": false }, "DNA repair inhibitor": { "total": 16, "is_approved": false } }, "approved_mechanism_pct": 25.9, "novel_mechanism_pct": 20.8, "mixed_pct": 14.8 }, "novel_target_identification": { "top_10_novel_targets": [ { "target": "MET", "trial_count": 363, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "PD-1", "trial_count": 100, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "MGMT", "trial_count": 63, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "EGFR", "trial_count": 61, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "mTOR", "trial_count": 42, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "IDH", "trial_count": 37, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "PD-L1", "trial_count": 25, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "PARP", "trial_count": 23, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "CTLA-4", "trial_count": 20, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "ALK", "trial_count": 19, "is_approved_for_gbm": false, "classification": "Novelty" } ], "replacement_targets": [ { "target": "VEGF", "trial_count": 200, "is_approved_for_gbm": true, "classification": "Replacement" } ], "all_novel_targets": [ { "target": "MET", "trial_count": 363, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "PD-1", "trial_count": 100, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "MGMT", "trial_count": 63, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "EGFR", "trial_count": 61, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "mTOR", "trial_count": 42, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "IDH", "trial_count": 37, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "PD-L1", "trial_count": 25, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "PARP", "trial_count": 23, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "CTLA-4", "trial_count": 20, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "ALK", "trial_count": 19, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "CDK", "trial_count": 17, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "TERT", "trial_count": 8, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "BRAF", "trial_count": 7, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "MEK", "trial_count": 7, "is_approved_for_gbm": false, "classification": "Novelty" }, { "target": "PI3K", "trial_count": 6, "is_approved_for_gbm": false, "classification": "Novelty" } ], "summary": { "total_targets": 16, "novel_count": 15, "replacement_count": 1 } }, "phase_attrition_analysis": [ { "target": "MET", "early_phase1": 18, "phase1": 165, "phase2": 170, "phase3": 26, "early_phase_total": 353, "phase3_to_early_ratio": 0.074, "progression_assessment": "Moderate" }, { "target": "PD-1", "early_phase1": 3, "phase1": 48, "phase2": 63, "phase3": 6, "early_phase_total": 114, "phase3_to_early_ratio": 0.053, "progression_assessment": "Moderate" }, { "target": "MGMT", "early_phase1": 1, "phase1": 24, "phase2": 36, "phase3": 11, "early_phase_total": 61, "phase3_to_early_ratio": 0.18, "progression_assessment": "High" }, { "target": "EGFR", "early_phase1": 4, "phase1": 41, "phase2": 20, "phase3": 3, "early_phase_total": 65, "phase3_to_early_ratio": 0.046, "progression_assessment": "Low" }, { "target": "mTOR", "early_phase1": 4, "phase1": 28, "phase2": 23, "phase3": 1, "early_phase_total": 55, "phase3_to_early_ratio": 0.018, "progression_assessment": "Low" } ], "literature_sentiment_analysis": [ { "target": "MET", "articles_mentioning_target": 72, "articles_with_negative_sentiment": 36, "negative_ratio": 0.5, "risk_level": "High", "sample_negative_articles": [ { "pmid": "36394838", "title": "Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival ", "negative_keywords": [ "poor" ] }, { "pmid": "35135556", "title": "Glioma targeted therapy: insight into future of molecular approaches.", "negative_keywords": [ "fail", "failure" ] }, { "pmid": "38438346", "title": "Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeos", "negative_keywords": [ "poor" ] } ] }, { "target": "PD-1", "articles_mentioning_target": 32, "articles_with_negative_sentiment": 19, "negative_ratio": 0.59, "risk_level": "High", "sample_negative_articles": [ { "pmid": "35135556", "title": "Glioma targeted therapy: insight into future of molecular approaches.", "negative_keywords": [ "fail", "failure" ] }, { "pmid": "40016450", "title": "Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma.", "negative_keywords": [ "limited efficacy" ] }, { "pmid": "32253714", "title": "A review of glioblastoma immunotherapy.", "negative_keywords": [ "fail", "failure", "disappointing" ] } ] }, { "target": "MGMT", "articles_mentioning_target": 15, "articles_with_negative_sentiment": 8, "negative_ratio": 0.53, "risk_level": "High", "sample_negative_articles": [ { "pmid": "36394838", "title": "Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival ", "negative_keywords": [ "poor" ] }, { "pmid": "38502052", "title": "Marizomib for patients with newly diagnosed glioblastoma: A randomized phase 3 trial.", "negative_keywords": [ "did not improve" ] }, { "pmid": "39480453", "title": "Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated Glioblastoma: A Rando", "negative_keywords": [ "poor" ] } ] }, { "target": "EGFR", "articles_mentioning_target": 11, "articles_with_negative_sentiment": 7, "negative_ratio": 0.64, "risk_level": "High", "sample_negative_articles": [ { "pmid": "35135556", "title": "Glioma targeted therapy: insight into future of molecular approaches.", "negative_keywords": [ "fail", "failure" ] }, { "pmid": "38899374", "title": "Current status of precision oncology in adult glioblastoma.", "negative_keywords": [ "fail", "failed", "poor" ] }, { "pmid": "35096619", "title": "Interactions Between Anti-Angiogenic Therapy and Immunotherapy in Glioblastoma.", "negative_keywords": [ "fail", "failed", "failure" ] } ] }, { "target": "mTOR", "articles_mentioning_target": 5, "articles_with_negative_sentiment": 3, "negative_ratio": 0.6, "risk_level": "High", "sample_negative_articles": [ { "pmid": "36825454", "title": "Top advances of the year: Neuro-oncology.", "negative_keywords": [ "fail", "failed" ] }, { "pmid": "38899374", "title": "Current status of precision oncology in adult glioblastoma.", "negative_keywords": [ "fail", "failed", "poor" ] }, { "pmid": "36408162", "title": "Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell deat", "negative_keywords": [ "limited efficacy" ] } ] } ], "key_gaps": [ { "gap_id": 1, "title": "Immunotherapy Pipeline vs. Approvals Mismatch", "description": "682 immunotherapy trials but 0 approved agents", "severity": "High" }, { "gap_id": 2, "title": "Novel Targets Show Limited Phase 3 Progression", "description": "Most novel targets have <0.1 Phase 3/Early Phase ratio, indicating significant pipeline attrition", "severity": "High" }, { "gap_id": 3, "title": "Over-Reliance on Approved Mechanism Classes", "description": "25.9% of trials are Replacements (same targets) rather than Novelties", "severity": "Moderate" } ] }