Table 1.

Selected phase II and III, finished or ongoing, clinical trials of anti-angiogenic therapy in glioblastoma, alone or in combination with other treatments.

Clinical Trial Reference	Intervention	Mechanism of Action	Patient Population	Design	Primary Endpoint	PFS	Conclusion
Sharma et al. 2019 [74]	Dovitinib	Tyrosine-kinase receptor inhibitor	Recurrent or Progressive GBM	Phase II, non-randomized, parallel	PFS 6 months	PFS-6 12% in anti-angiogenic naïve and 0% in anti-angiogenic exposed	Dovitinib was not efficacious in recurrent GBM
Bota et al. 2021 [75]	Marizomib	Panproteanoma inhibitor + monoclonal antibody anti-VEGF	Recurrent or Progressive GBM	Phase II, non-randomized, intra-patient dose escalation	PFS 6 months	PFS-6 29.8% OS 9.1 months	No benefit of the addition of marizomib to bevacizumab
Cloughesy et al. 2020 [76]	VB-111 + bevacizumab	Oncolytic virus + anti-VEGF	Recurrent GBM	Phase III	OS	OS 6.8 months	No benefit and higher rates of adverse events
Brenner et al. 2021 [77]	Evofosfamide + bevacizumab	hypoxia activated pro-drug + anti-VEGF	Recurrent GBM	Phase II single-arm	Safety	PFS-4 31% OS 4.6 months	Deserves further investigation
Lee et al. 2021 [78]	Trebananib + bevacizumab	Sequester Ang1/Ang2 + anti-VEGF	Recurrent GBM	Phase II randomized	PFS 6 months	PFS-6 22.6%	Detrimental (lower PFS than bevacizumab alone)
STELLAR NCT03025893 [79]	Sunitinib	Tyrosine-kinase receptor inhibitor	Recurrent GBM	Phase II/III randomized, against lomustine	PFS	Ongoing	-
NCT04952571 [80]	Camrelizumab + Bevacizumab	Anti-PD1 + anti-VEGF monoclonal antibodies	Recurrent GBM	Phase II non-randomized, parallel	PFS	Ongoing	-

GBM, glioblastoma; OS, overall survival; PFS, period of free survival.