Table 2:

Current Clinical Trial Outcomes for Glioma Therapeutics

Targeted therapy	Mechanism	GBM setting	Phase	Clinical trial identifier	Outcomes
Ad-hCMV-TK+ Ad-hCMV-Flt3L	Combined direct tumor cell killing and immune stimulation	Newly diagnosed GBM	Phase 1	NCT01811992	A dose escalation safety study has recently concluded enrolling patients harboring primary GBM, that were treated with both vectors delivered simultaneously into the peritumoral region after tumor resection and results are expected by the end of 2020.
HSV-TK	Direct tumor cell killing	Newly diagnosed GBM	Phase 2	NCT00002824	Did not show an increase in the median overall survival.
Nivolumab + Bevacizumab	Anti-PD-1 + anti-VEGF	Recurrent GBM	Phase 3	NCT02017717	Did not show an increase in the median overall survival. Nivolumab alone did not demonstrate an improved overall survival compared with bevacizumab. Overall radiographic response was lower in nivolumab group compared to bevacizumab.
Ipilimumab and/or Nivolumab in Combination with Temozolomide	Anti-PD-1 + anti-CTLA4 + TMZ	Newly diagnosed GBM	Phase 1	NCT02311920	Ipilimumab and/or nivolumab are safe and tolerable with similar toxicity profiles when given with adjuavant TMZ for newly diagnosed GBM.
Toca 511	Combination retroviral encoding cytosine deaminase with targeted delivery of prodrug, 5-fluorocytosine	Recurrent GBM	Phase 3	NCT02414165	The trial did not meet the primary endpoint, demonstrating 11.1 months of overall median survival compared to 12.2 months with standard of care.
DNX-2401 (Delta-24-RGD-4C)	Tumor selective oncolytic adenovirus	Recurrent GBM	Phase 1	NCT00805376	Results demonstrated that Delta-23-RGD replicates and spreads within the tumor, leading to immunogenic tumor cell death and enhancement of T lymphocyte tumor infiltration.
ABT-806	EGFRvlll antibody	Advanced Solid tumors	Phase 1	NCT01472003 NCT01255657 NCT01406119	mAb806 has significant antitumor activity without nonspecific binding to normal tissues with safe and tolerable toxicity profile
IDH305	Mutant IDH1 small molecule inhibitor	Recurrent glioma with R132H mutation	Phase 1	NCT02381886	Lowered 2HG production by 70% after 1 week of treatment. Signs of tumor progression were identified based on FLAIR volume.
IDH305	Mutant IDH1 inhibitor	IDH1 Mutant Grade II or III Glioma	Phase 2	NCT02977689	Withdrawn after 1 year
SonicCould	Ultrasound Devise to open BBB	Recurrent GBM	Phase 2	NCT02253212	BBB was disrupted in 11 patients and they showed a median progression-free survival of 4.11 months and median over all survival of 12.94 months.
ABT-414	EGFRvIII antibody	Newly diagnosed and recurrent GBM	Phase 2/3	NCT02573324 NCT02343406	Randomized studies are ongoing to determine efficacy in newly diagnosed and recurrent glioblastoma
CDX-110-KLH + TMZ+ IR	EGFRvIII Vaccine	Newly diagnosed GBM	Phase 2	NCT00458601	The trial for this vaccine was terminated early as it was deemed likely that the study would fail to meet primary end point.
Pembrolizumab	Anti-PD1	Recurrent GBM	Phase 2	NCT03899857	Median progression-free survival was 7 months and progression-free survival at 6 months Median overall survival was not reached. Tumor microenvironment was enriched with CD68 macrophages but exhibited paucity of effector T cells.
CART-EGFRvIII + pembrolizumab	Autologous CAR-T targeted to the EGFR variant III plus PD-1 inhibition	Newly diagnosed GBM with EGFRvIII and unmethylatd MGMT	Phase 1	NCT03726515	There was variable response to CART-EGFRvIII therapy due to the inherent heterogeneity in GBM.
Autologous T-cells	Autologous CMV specific cytotoxic T-cells	Newly diagnosed and recurrent GBM	Phase 1/2	NCT02661282	Repeated infusions of CMV-TC were associated with a significant increase in circulating CMV+ CD8+ T-cells Adoptive infusion of CMV-TC after lymphodepleting therapy with MZ was well tolerated. The final dose level is currently being enrolled. Thereafter efficacy will be evaluated in cohorts of in newly diagnosed and recurrent GBM patients.
PVSRIPO	Oncolytic polio:rhinovirus recombiant virus	Recurrent GBM	Phase I	NCT01491893	Intratumoral infusion of PVSRIPO in patients with recurrent GBM confirmed the absence of neurovirulent potential.