Table 1.

Published clinical trials of oncolytic therapy for malignant glioma

Year	Phase	Generic name	Glioma type	Administration	Max-dose	mOS	Adverse events (attributing to OV)	References
HSV-1
2000	I	G207	rGBM:16 rAA:5	I.T	3 × 109 PFU	6.2	There was no AE attributing to OV treatment	Markert et al. [14]
2000	I	HSV1716	rGBM:8 rAA:1	I.T	1 × 105 PFU	9	There was no AE attributing to OV treatment	Rampling et al. [15]
2002	I	HSV1716	rGBM:11 rAA:1	I.T	1 × 105 PFU	6.5	There was no AE attributing to OV treatment	Papanastassiou et al. [16]
2004	I	HSV1716	rGBM:4 rAA:1 rAO:1 nGBM:6	I.C	1 × 105 PFU	11.25	There was no AE attributing to OV treatment	Harrow et al. [17]
2009	Ib	G207	rGBM:6	I.T *2	1.15 × 109 PFU	6.6	II: fever III: seizure, decreased mental status, increased temperature (max 39.7 °C), hemiparesis, neglect, intermittent seizure activity, somnolence, motor neuropathy, sided weakness	Markert et al. [18]
2014	I	G207	rGBM:7 rAA:2	I.T+RT	1.0 × 109 PFU	7.5	III: seizure, fever	Markert et al. [19]
2021	I	G207	rGBM:11 rAA:1	I.T+RT	1 × 108 PFU+5 Gy	12.2	I: diarrhea, nausea, vomiting, chills, fatigue, fever, anorexia, dizziness, headache, seizure, hemorrhage	Friedman et al. [20]
2022	II	G47Δ	rGBM:19	I.T *6	1 × 109 PFU	20.2	I: fever, vomiting, nausea, cerebral edema, neuropathy–sensory, headache, anemia, lymphocyte count decreased, white blood cell count decreased, platelet count decreased, bilirubin increased, γ-Glutamyl transpeptidase increased, PT-INR increased, hypoalbuminemia, hyponatremia II: fever, fatigue, vomiting, nausea, seizure, cerebral edema, lymphocyte count decreased, white blood cell count decreased, neutrophil count decreased III: fever, vomiting, headache, lymphocyte count decreased, white blood cell count decreased, neutrophil count decreased IV: lymphocyte count decreased	Todo et al. [10]
2022	I/II	G47Δ	rGBM:13	I.T *2	1 × 109 PFU	7.3	I: fever, headache, nausea, vomiting, decreased hemoglobin, hemorrhage with surgery II: vomiting, seizure, fever III: decreased leukocytes	Todo et al. [12]
Adenovirus
2004	I	ONYX- 015	rGBM:17 rAA 5 rAO 2	I.C	1 × 1010 PFU	6.2	There was no AE attributing to OV treatment	Chiocca et al. [21]
2018	I	DNX-2401	rGBM:33 rAA:2 rGliosarcoma:2	I.T/I.T-excision-I.C *2	3 × 1010 VP	13	I: headache, nausea, confusional state, vomiting, pyrexia	Lang et al. [22]
2021	I	NSC-CRAd-S-pk7	nGBM:11 nAA:1	I.C	1.875 × 1011VP/ 1.50 × 108 NSC	18.4	II: subdural fluid collection III: meningitis	Fares et al. [23]
2022	I	DNX-2401	nDIPG:12	I.T+RT	5 × 1010 PFU	17.8	I: vomiting, fever, nausea, trigeminal nerve disorder, dizziness, facial nerve disorder II: fever, somnolence, headache, nystagmus III: neurological deterioration	Larraya et al. [24]
2022	I	DNX-2401	rGBM:19	I.T CED	1 × 1011 VP	4.3	Only reported the relationship of SAE with treatment: III: seizure, increased intracranial pressure, meningitis with hydrocephalus, increased intracranial pressure IV: confusion	Putten et al. [25]
2023	I/II	DNX-2401	rGBM:49	I.T+ pembrolizumab	5 × 1010 VP	12.5	I: brain edema, headache, fatigue, dysphasia, pyrexia, decreased appetite, myalgia, nausea II: brain edema, headache, fatigue, dysphasia, hemiparesis, decreased appetite, myalgia, nausea III: brain edema, headache, hemiparesis IV: brain edema	Nassiri et al. [26]
Reovirus
2008	I	Reovirus	rGBM:9 rAA:2 rAO:1	I.T-excision	7 × 108 PFU	5.25	III: GGT increasing	Forsyth et al. [27]
2014	I	Reovirus	rGBM:15	I.T CED	1 × 1010 PFU	4.6	There was no AE attributing to OV treatment	Kicielinski et al. [28]
H-1 parvovirus
2017	I/IIa	ParvOryx	rGBM:18	I.T-excision-I.C/I.V-excision-I.C *2	5 × 109 PFU	15.5	There was no AE attributing to OV treatment	Geletneky et al. [29]
Recombinant poliovirus
2018	I	PVSRIPO	rGBM:61	I.T CED	7 × 109 PFU	12.5	I: blurred vision, diplopia, focusing difficulty, visual field cut or hemianopia, nausea, vomiting, fatigue, gait disturbance, cognitive disturbance, dystonia, facial muscle weakness, headache, intracranial hemorrhage, paresthesia, pyramidal tract syndrome, seizure, confusion, hallucinations, urinary incontinence II: visual field cut or hemianopia, fatigue, cognitive disturbance, dysphasia, headache, pyramidal tract syndrome, seizure, confusion, vascular disorder, hypertension III: gait disturbance, dystonia, headache, pyramidal tract syndrome, seizure, confusion, delusions IV: cerebral edema V: seizure	Desjardins et al. [30]
Newcastle disease virus
2006	I/II	NDV-HUJ	rGBM:11	I.V. *3	5.5 × 1010 EID50	8	I: fever II: fever	Freeman et al. [31]