Table 6. Combination immunotherapy clinical trials.

Trial number	Abbreviated trial name	Target	Study design	Population	Intervention/arms	Control	Number of analyzed patients	Survival, median months (95% CI)	Additional outcomes	Trial status	Reference
Vaccine + ICI
NCT04013672	SurVaxM peptide vaccine and pembrolizumab	Survivin, PD-1	Phase II, 2 arms	Adults, recurrent GBM	SurVaxM/GM-CSF/Montanide ISA 51 every 2 weeks times 4 then every 3 months, with pembrolizumab every 3 weeks, until progression or intolerance; Arm I: anti-PD-1 therapy naïve; Arm II: failed previous anti-PD-1 therapy	None	51 expected	N/A	Primary: PFS; secondary: toxicity	Recruiting	N/A
NCT03893903	AMPLIFY-NEOVAC	IDH1R132H, PD-L1	Phase I, 3 arms, randomized	Adults, recurrent HGG excluding 1p/19q co-deletion and nuclear ATRX loss	Experimental drug every 2 weeks ×3, followed by re-resection, followed by maintenance experimental drug: Arm I: IDH1R132H peptide vaccine; Arm II: IDH1R132H peptide vaccine with avelumab; Arm III: avelumab	None	48 expected	N/A	Primary: RLT; secondary: immunogenicity, AEs, ORR, OS, PFS	Recruiting	N/A
NCT03665545	IMA950-106	11 GBM TAAs, PD-1	Phase I/II, 2 arms, randomized	Adults, recurrent GBM, HLA-A*02(+)	Arm I: IMA950/poly-ICLC vaccine alone; Arm II: IMA950/poly-ICLC vaccine with pembrolizumab	None	24 expected	N/A	Primary: toxicity; secondary: PFS, OS, QoL, immunogenicity	Recruiting	N/A
NCT03018288	Pembrolizumab +/− HSPPC-96 vaccine	PD-1, HSPPC-96	Phase II, randomized, double-blind	Adults, new GBM	Arm I: pembrolizumab every 3 weeks ×3 concomitant with standard chemoRT with TMZ; Arm II: Arm I with addition of HSPPC-96 vaccine post-chemoradiation weekly ×4, then every 3 weeks ×6	Arm III: Arm II with placebo vaccine	14 enrolled	N/A	Primary: OS	Suspended (root cause analysis being conducted)	N/A
NCT04201873	Autologous tumor lysate DC vaccine +/− pembrolizumab	Tumor lysate (autologous), PD-1	Phase I, randomized	Adults, recurrent GBM	Pembrolizumab ×1 2 weeks prior to re-resection, then every 3 weeks after resection until progression or intolerance. DC vaccine/poly-ICLC after resection every 2 weeks ×3	Placebo pembrolizumab with experimental DC vaccine/poly-ICLC on same schedule	40 expected	N/A	Primary: toxicity, immunogenicity; secondary: OS, PFS, biomarkers	Recruiting	N/A
NCT02529072	AVeRT	pp65, PD-1	Phase I, randomized	Adults, recurrent HGG	Arm I: nivolumab every 2 weeks ×4, then re-resection, then biweekly nivolumab until progression and monthly CMV pp65 DC vaccine ×5; Arm II: Nivolumab every 2 weeks ×4, then nivolumab and CMV pp65 DC vaccine every 2 weeks ×3, then re-resection, then biweekly nivolumab until progression and monthly CMV pp65 DC vaccine ×5	None	Arm I: 3; Arm II: 3	PFS, OS: Arm I: 4.3 (2.1–5.3), 8.0 (5.7–8.3); Arm II: 6.3 (4.7–10.7), 15.3 (4.73–not reached)	–	Completed, unpublished data	(182)
NCT02798406	DNX-2401 oncolytic adenovirus and pembrolizumab	E1A mutant, PD-1	Phase II, single arm	Adults, recurrent GBM	DNX-2401 vaccine intratumoral injection ×1, then pembrolizumab every 3 weeks for 2 years or until progression or intolerance	None	49 enrolled	N/A	Primary: ORR; secondary: OS, PFS	Active, not recruiting	N/A
Vaccine + other
NCT02366728	ELEVATE	pp65, IL-2R	Phase II, randomized, double-blind, placebo-controlled	Adults, new GBM s/p resection with <1 cm residual in maximal dimension	Arm I: placebo DC vaccine; Arm II: DC vaccine; Arm III: DC vaccine with basiliximab (anti-IL-2R)	Arm I: placebo vaccine	100 expected	N/A	Primary: OS, immunogenicity; secondary: PFS	Active, not recruiting	N/A
Vaccine + ALT
N/A	Autologous whole tumor vaccine and anti-CD3 T cells	Tumor antigens, CD3	Phase I, single arm	Adults, recurrent HGG	Re-resection followed by vaccine/GM-CSF ×2, followed by activated T cells ×1	None	19	OS: 12 mo (range, 6–28)	–	Published	(181)
NCT00693095	CMV-specific T cells +/− CMV pp65 DC vaccine	pp65	Phase I, randomized	Adults, new GBM	Arm I: activated T cells ×1 and DC vaccine every 2 weeks ×3 concomitant with standard adjuvant TMZ; Arm II: Arm I with saline placebo instead of DC vaccine	None	Arm I: 9; Arm II: 8	PFS and OS N/R; polyfunctional T cells correlated with OS (R =0.7371, P=0.0369) in Arm I	G3+ AEs: 0	Published	(180)
ALT + ICI
NCT03726515	EGFRvIII CAR T cells and pembrolizumab	EGFRvIII, PD-1	Phase I, single arm	Adults, new GBM, MGMT-unmethylated, EGFRvIII(+)	2–3 weeks after short-course RT (40 Gy/15 fx) without TMZ, CAR T cells and pembrolizumab given every 3 weeks ×3 and ×4, respectively	None	7 expected	N/A	Primary: toxicity; secondary: OS, PFS, ORR	Active, not recruiting	(178)
NCT04003649	IL13Rα2 CAR T cells and nivolumab +/− ipilimumab	IL13Rα2, PD-1, CTLA-4	Phase I, randomized	Adults, recurrent GBM, IL13Rα2(+)	Re-resection with intraventricular catheter placement, then: Arm I: ipilimumab and nivolumab ×1, then two weeks later, nivolumab and intraventricular CAR T cells ×4 or more; Arm II: nivolumab and intraventricular CAR T cells ×4 or more	None	60 expected	N/A	Primary: toxicity, feasibility; secondary: OS, PFS, ORR, immunogenicity, biomarkers, QoL	Recruiting	N/A
ICI + other
NCT02423343	Galunisertib (anti-TGFβRI) and nivolumab	PD-1, TGFβRI	Phase Ib, single arm	Adults, recurrent GBM	Galunisertib for 14 days every 4 weeks ×4 and nivolumab every 2 weeks ×8	None	75 enrolled (entire cohort)	N/A	Primary: MTD	Active, not recruiting	N/A
NCT04160494	D2C7 (EGFR-targeted immunotoxin) and atezolizumab	EGFRwt/EGFRvIII, PD-L1	Phase I, single arm	Adults, recurrent GBM	Intratumoral D2C7 ×1, then atezolizumab ×1 2 weeks later, then possible re-resection 2 weeks later, then atezolizumab every 3 weeks for 2 years or until progression or intolerance	None	18 expected	N/A	Primary: toxicity	Recruiting	N/A

ICI, immune checkpoint inhibitor; PD-1, programmed death-1; GBM, glioblastoma; GM-CSF, granulocyte-macrophage colony-stimulating factor; PFS, progression-free survival; PD-L1, programmed death ligand 1; HGG, high grade glioma (i.e., WHO Grade III or IV glioma); ATRX, alpha-thalassemia/mental retardation, X-linked; RLT, regime limiting toxicity; AE, adverse event; ORR, objective response rate; OS, overall survival; TAA, tumor associated antigen; Poly-ICLC, polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose; QoL, quality of life; HSPPC-96, heat shock protein peptide complex 96; ChemoRT, chemoradiation; TMZ, temozolomide; DC, dendritic cell; pp65, phosphoprotein 65; CMV, cytomegalovirus; E1A, early region 1A; IL-2R, interleukin 2 receptor; N/R, not reported; G3, grade 3; MGMT, O⁶-methylguanine DNA methyltransferase; EGFRvIII, epidermal growth factor variant III; RT, radiation; Gy, Gray; fx, fractions; CAR, chimeric antigen receptor; IL13Rα2, interleukin 13 receptor subunit alpha 1; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; TGFβRI, TGFβ receptor I; MTD, maximum tolerated dose; EGFRwt, epidermal growth factor wild type.