Table 1.

Select clinical trials exploring therapeutic vaccine strategies in gliomas.

Disease	Phase	Target	Vaccine strategy	Status	Primary endpoint	Results	Toxicities
GBM, newly diagnosed	I	NeoVax: Personalized neoantigen	Long peptide vaccine with concurrent  RTX  TMZ  Pembro-lizumab	Recruiting, est. completion date: 2026	Safety, biological activity	mPFS 7.6 months, mOS 16.8 months 34	No DLT
GBM, newly diagnosed	I	GAPVAC: Personalized neoantigen	2 peptide vaccines (APVAC-1 & APVAC-2) with concurrent  CRT  Maintenance TMZ	Completed	Safety, biological activity, and feasibility	mPFS 14.2 months, mOS 29 months 35	Anaphylaxis (n = 2), cerebral edema (n = 1)
GBM, newly diagnosed	I	NeoVax: Personalized neoantigen	Peptide vaccine with concurrent  nivolumab  ipilimumab	Terminated	Safety, feasibility	N/A	N/A
GBM, newly diagnosed	III	Rindo-pepimut: EGFRvIII	Peptide vaccine with concurrent  TMZ	Terminated for futility	OS	mOS 20.1 months 36	Grade 3 or 4 AEs (treatment versus control): thrombo-cytopenia [32 (9%) versus 23 (6%)], fatigue [6 (2%) versus 19 (5%)], brain edema [8 (2%) versus 11 (3%)], seizure [nine (2%) versus eight (2%)], and headache [6 (2%) versus 10 (3%)]. 16 deaths in the study were caused by AEs [nine (4%) and seven (3%)]
GBM, relapsed, EGFRvIII-expr.	II	Rindo-pepimut: EGFRvIII	Peptide vaccine with concurrent  bevacizumab	Completed	PFS rate, objective response rate	PFS6 28% for treatment, versus 16% for control; mDOR of 7.8 months versus 5.6 months; ability to discontinue steroids for 6 months (33% versus 0%) 37	Grade 3 or 4 events considered related to Rindopepimut: increase in alanine amino-transferase (n = 1), increase in gamma – glutamyl transferase (n = 1)
GBM, newly diagnosed	IIa	SurVaxM: Survivin	Peptide vaccine with concurrent  TMZ	Active, not recruiting, est. completion date: 2023	6-month PFS	mPFS 11.4 months, mOS 25.9 months 38	No serious AEs
GBM, newly diagnosed	II	UCPVax-Glio: TERT	Peptide vaccine with concurrent  TMZ	Recruiting, est. completion date: 2023	Immuno-genicity	N/A	N/A
GBM, newly diagnosed	I	GNOS-PV01: Personalized neoantigen DNA	DNA vaccine with CELLECTRA®2000 EP Device, plasmid encoded IL-12 and concurrent  RTX	Active, not recruiting, est. completion date: 2023	Safety, tolerability, and feasibility	N/A	N/A
GBM, newly diagnosed	I	Total tumor mRNA, pp65 CMV	RNA loaded lipid particle with concurrent  CRT	Recruiting, est. completion date: 2026	Feasibility, safety, maximum tolerated dose	N/A	N/A
GBM, recurrent	I/II	WT1	DC vaccine with concurrent  TMZ	Recruiting, est. completion date: 2026	OS	N/A	N/A
GBM, recurrent	I	CD133	DC vaccine pulsed with peptide antigen	Completed	Safety, tolerability	Safe and well tolerated 39	N/A
GBM, newly diagnosed	I/II	pp65 CMV	DC vaccine with Td toxoid preconditioning and concurrent  TMZ	Active, not recruiting, est. completion date: 2022	Feasibility, safety	mOS 41.1 months40–42	N/A
GBM, newly diagnosed	II	pp65 CMV	CMV RNA-Pulsed Dendritic Cells with Td toxoid preconditioning	Recruiting, est. completion date: 2024	Change in mOS	N/A	N/A
GBM, recurrent	I	pp65 CMV	DC vaccine with concurrent  nivolumab	Terminated	Safety	N/A	Grade IV: wound infection (n = 2), meningitis (n = 1) 43
GBM, newly diagnosed	II	ICT-107: AIM-2, MAGE-1, TRP-2, gp100, HER-2, IL-13Ra2	DC vaccine pulsed with immunogenic antigens	Completed	OS	mOS 17.0 months, mPFS 11.2 months44,45	Overall well tolerated, no difference in toxicity between treatment groups
GBM, newly diagnosed	III	ICT-107: AIM-2, MAGE-1, TRP-2, gp100, HER-2, IL-13Ra2	DC vaccine pulsed with immunogenic antigens	Suspended for lack of funding	OS	N/A	N/A
GBM, newly diagnosed	III	DCVax-L: tumor lysate	DC vaccine with concurrent  TMZ	Completed	OS	mOS 23.1 months from surgery 46	Grade 3 or 4 AEs in 2.1% of ITT patients (n = 7)
GBM, newly diagnosed	I	Tumor lysate	DC vaccine with imiquimod pretreatment	Completed	Treatment-related AEs	N/A	N/A
GBM, recurrent	I	Tumor lysate	DC vaccine with concurrent  Pembro-lizumab	Recruiting	Cell cycle-related signature, expansion of T cell receptor clones, incidence of AEs	N/A	N/A
GBM, newly diagnosed or recurrent	I	GSC cell line lysate	DC vaccine with concurrent  TMZ  RTX  bevacizumab	Completed	Safety, tolerability, number of serious AEs, treatment-related toxicities	Newly diagnosed group: mPFS 8.75 months, mOS 20.36 months; recurrent group: mPFS 3.23 months, mOS 11.97 months 47	No grade 3 or 4 toxicity
GBM, recurrent or pro-gressive	I/II	gp96 heat shock protein-peptide complex	Peptide vaccine	Completed	Safety, tolerability, time to disease recurrence and pro-gression, OS	mOS 42.6 weeks, mPFS 19.1 weeks 48	1 grade 3 event directly attributable to the vaccine (fatigue)
GBM, newly diagnosed	II	gp96 heat shock protein-peptide complex	Peptide vaccine	Completed	1-year OS	N/A	N/A
GBM, newly diagnosed	II	pp65 CMV	DC vaccine with Td toxoid preconditioning and concurrent  TMZ  basiliximab	Completed	mOS, percentage of 111In-labeled dendritic cells migrating to the inguinal lymph nodes	Migration of vaccinating DCs to draining lymph nodes 41	N/A
GBM, newly diagnosed or recurrent	II	Tumor lysate	DC vaccine	Active, not recruiting, est. completion date: 2025	Most effective combi-nation of DC vaccine com-ponents	N/A	N/A
IDHm glioma	I	IDH1R132H	Peptide vaccine	Completed	Safety and tolerability assessed by regime limiting toxicity, immuno-genicity	3-year PF rate 0.63, 3-year death-free rate 0.83, 2-year PFS among patients with immune responses 49	No grade 2–4 vaccine-related events
IDHm glioma, pro-gressive	I	IDH1R132H	Peptide vaccine	Recruiting, est. completion date: 2024	Safety and tolerability assessed by regime limiting toxicity	N/A	N/A
IDHm glioma, recurrent, grade II	I	IDH1R132H	Peptide vaccine with Td toxoid preconditioning and concurrent  TMZ	Completed	Percentage of participants with un-acceptable toxicity	Induced specific immune responses 50	Grade 2 injection site reaction (n = 1)
DMG; pediatric HGG; medullo-blastoma	II	pp65 CMV	Peptide vaccine with Td toxoid preconditioning and concurrent  TMZ	Not yet recruiting	PFS and OS	N/A	N/A
DMG; pediatric HGG; medullo-blastoma	I	SurVaxM: Survivin	Peptide vaccine	Recruiting, est. completion date: 2028	Toxicity	N/A	N/A
DMG; pediatric HGG	I/II	WT1	mRNA-loaded DC vaccine with concomitant  CRT	Active, not recruiting, est. completion date: 2027	Safety, feasibility	N/A	N/A
DMG, H3K27M-altered	I	16 neoepitopes	Neoantigen heat shock protein vaccine with concomitant  balstilimab  zalifrelimab	Recruiting, est. completion date: 2025	Safety and tolerability	N/A	N/A
DMG, H3K27M-altered	I/II	K27M peptide	Peptide vaccine with concomitant  nivolumab	Active, not recruiting, est. completion date: 2024	AEs, OS	mOS 16.1 months for responder 51	No grade-4 AEs
H3-mutated glioma, newly diagnosed	I	K27M peptide	Peptide vaccine with imiquimod pretreatment	Recruiting, est. completion date: 2025	Safety and immuno-genicity	N/A	N/A
DMG	I	Tumor cell-line lysate	DC vaccine	Completed	Number of serious AEs per patient	Specific immune responses in n = 8/9 patients 52	Intratumoral hemorrhage (n = 1), osteomyelitis grade 3 (n = 1)

AE, adverse event; CMV, cytomegalovirus; CRT, chemo-radiation therapy; DCs, dendritic cells; DLT, dose-limiting toxicity; DMGs, diffuse midline gliomas; EGFR, epidermal growth factor receptor; EGFRvIII, EGFR variant III; GBM, glioblastoma; HGG, high-grade glioma; IDHm, isocitrate dehydrogenase mutant; ITT, intention-to-treat; mDOR, median duration of response; mOS, median overall-survival; mPFS, median progression-free survival; PFS6, progression-free survival at 6 months; PF rate, progression-free rate; RTX, radiotherapy; TERT, telomerase reverse transcriptase; Td toxoid, tetanus-diphtheria toxoid; TMZ, temozolomide.