Table 1.
Selected ADCs, immunotoxins and radioimmunoconjugates in high grade gliomas.
| Drug | Class | Phase | Date | Toxicities | Efficacy | Comments |
|---|---|---|---|---|---|---|
| ADCs i | ||||||
| ABT-414 (14) | Anti-EGFR ADC with MMAF | I | 2015 | Lymphopenia, ocular toxicity, brain oedema, increased transaminases | Monotherapy: RR 8%, mOS N/A, PFS-6 24% | Data in EGFR amplified. Phase 2 and 3 studies in progress |
| With TMZ: RR 17%, mOS N/A, PFS-6 25% | ||||||
| AMG-595 (15) | Anti-EGFR ADC with DM1 | I | 2014 | Thrombocytopenia, LFT abnormalities | RR 8%; mOS N/A; PFS-6 N/A | |
| Immunotoxins | ||||||
| Cintredexin Besudotoxin (16) | IL13–PE38QQR | III | 2010 | Pulmonary embolism (8% including one fatal) | RR N/A; mOS 11.3 months; PFS-6 N/A | |
| NBI-3001 (17) | Circularized IL4–PE38KDEL | I/II | 2003 | Neurological deficits (Weakness, aphasia, confusion, coma), seizures, headaches, cerebral oedema, nausea, meningitis) | RR N/A; mOS 5.8months*; PFS-6 48% | |
| TP-38 (IVAX) (18) | TGFα + PE38 | I | 2008 | Fatigue, neurological deterioration (seizures, hemiparesis) | RR 13%; mOS 5 months*; PFS-6 N/A | |
| Tf-CRM107 (19) | Transferrin-DT | II | 2003 | Cerebral oedema, seizures | RR 35%; mOS 9 months; PFS-6 N/A | Phase 3 studies were aborted or remain unreported (20) |
| Radioimmunoconjugates | ||||||
| 125I-Mab 425 (21) | IV murine anti-EGFR (with RT-TMZ) | II | 2010 | Occasional nausea, flushing, hypotension, skin irritation. Only 4 pts had HAMA | RR N/A; mOS 20.4 months | A sequential cohort with RT alone had mOS 10.2 months |
| 131I-81C6 (22) | LR murine anti-tenascin (with RT-chemo) | Pilot | 2008 | Seizures (including status epilepticus), haematological, neurological, infective, thrombotic | RR N/A; mOS 22.6 months | |
| 131I-BC2/BC4 (23) | LR murine anti-tenascin (with conventional surgery and post-operative treatment) | I/II | 1999 | Headaches, HAMA reactions | RR N/A; mOS 19 months | Data shown for GBM patients; mOS was 25 months in small volume disease |
ADC, Antibody drug conjugate; EGFR, Epidermal growth factor receptor; HAMA, human anti–mouse antibody; LFTs, liver function tests; mOS, median overall survival; mPFS, median progression free survival; N/A; Not Available, RR, Response rate; RT, Radiotherapy; TMZ, temozolomide.