Table 2. Summary of phase I trials of targeted therapy for rGBMs.
| References | No. | Therapeutic target | Therapy | Protocol | Result | Beneficial subgroup | Adverse effects | Conclusions | |
| All grade | ≥grade 3 | ||||||||
| FAK, focal adhesion kinase; CTO, carboxyamidotriazole orotate; ORR, objective response rate; mOS, median overall survival; mPFS, median progression-free survival; EGFR, epidermal growth factor receptor; BBB, blood-brain barrier; NA, not available. | |||||||||
| Brown NF
et al. 2018 (78) |
13 | FAK | GSK2256098 | Dose-escalation
(1,000 mg, 750 mg, 500 mg) |
ORR 0 | / | 13 | 6 | Effective in crossing the BBB and enter tumor |
| Omuro A
et al. 2018 (79) |
27 | Non-voltage dependent calcium channels | CTO | Dose-escalation
(219−812.5 mg/m2) |
ORR 26% (7/27);
mOS 10.2 months; 1-year OS 46%; mPFS 3.1 months; 6-month PFS 37% |
EGFR amplification | NA | 0 | CTO can combine safely with temozolomide, favorable BBB penetration |
| Wen PY
et al. 2020 (46) |
33 | PI3K/mTOR | GDC-0084 | Dose-escalation (2−65 mg) | ORR 0 | / | 33 | 9 | Effective in crossing the BBB |
| Kaley TJ
et al. 2020 (80) |
17 | mTOR/AKT | Temsirolimus + perifosine | Dose-escalation
(T: 15−170 mg; P: 600 mg → 900 mg) |
mOS 10.4 months;
mPFS 2.7 months |
/ | NA | NA | Combination therapy is tolerable in heavily pretreated patients |
| Reardon DA
et al. 2020 (81) |
14 | Indoleamine 2, 3-dioxygenase (IDO1) | PF-06840003 | Dose-escalation (125 mg, 250 mg, 500 mg) | ORR 0;
mPFS 1.9−2.8 months |
/ | 14 | 4 | Well tolerated, pharmacodynamic effect and durable clinical benefit |