Table 1 Available completed and ongoing clinical trials of tumor vaccine therapy for recurrent glioblastoma

Rindopepimut + TMZ

EGFR-VIII peptide vaccine

NCT01498328

(ReACT trial)

II

Relapsed EGFR vIII-positive GBM

73

Open label

Double-blind

Two arms

Primary outcome, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary endpoints favored the rindopepimut group, including a statistically significant survival extension, a higher overall response rate of 30%, a longer median duration of response, and the better ability to discontinue steroids for ≥ 6 months

[103]

HSPPC-96

HSP vaccine

NCT02722512

I

Recurrent resectable intracranial GBM

12

Open label Dose escalation

Cohort expansion

No adverse events attributable to the vaccine were found. Testing of peripheral blood leukocytes before and after vaccination revealed a significant peripheral immune response specific for the peptides bound to HSP-96, in 11 of the 12 patients treated. The response time lasted 47 weeks for those patients having positive immune response

[105]

HSPPC-96

HSP vaccine

NCT00293423

I/II

Relapsed GBM

41

Open label

Dose escalation

Single arm

Median overall survival was 42.6 weeks (95% CI 34.7–50.5). Twenty-seven (66%) patients were lymphopenic prior to therapy, and patients with lymphocyte counts below the cohort median demonstrated decreased overall survival. No treatment-related severe side effects

[104]

HSPPC-96 + Bevacizumab

HSP vaccine

NCT01814813

II/III

Surgically resectable rGBM

90

Open label

Double-blind

Three arms

Ongoing

[109]

SruVaxM + Sargramostim

survivin vaccine

NCT01250470

I

Survivin-positive recurrent glioma

9

Open label

Dose escalation

SurVaxM was well tolerated with mostly grade one adverse events and no serious adverse events attributable to the study drug. 6 of 9 had a cellular response and 3 of 9 achieved a local response. The median PFS of all patients was 17.6 weeks, and the median OS reached 88.6 weeks with 7 patients surviving more than 12 months

[111]

SurVaxM + Pembrolizumab

Survivin vaccine

NCT04013672

II

rGBM

40

Open label

Double-blind

Two arms

Ongoing

[112]

SL-701 + poly-ICLC

Glioma-associated antigen vaccine

NCT02078648

I/II

rGBM

74

Open label

Dose escalation

Single arm

Ongoing

[115]

IMA950/Poly-ICLC + Pembrolizumab

Multipeptide vaccine

NCT03665545

I/II

Relapsing GBM

24

Open label

Dose escalation

Two arms

Ongoing

[116]

EO2041 + Nivolumab + Bevacizumab

Multipeptide vaccine

NCT04116658

Ib/IIa

Progressive or first recurrent GBM

76

Open label

Dose escalation

Three arms

All patients have been well tolerated through injections. The biosecurity feature of EO2401 was almost the same as nivolumab. Robust immune response has been observed in EO2401 plus nivolumab group. The median PFS of EO2401 combined with nivolumab and standardized bevacizumab group was 5.5 months, and median OS was 12.2 months

[117]

HLA-A24–restricted vaccine candidates (ITK-1)

Multipeptide vaccine

UMIN000001243

I

Recurrent or progressive supratentorial GBM

12

Open label

Dose escalation

Cohort expansion

No serious adverse drug reactions were encountered, and treatment was well tolerated. The vaccine induced dose-dependent immune boosting with a response rate of 16.7%. The recommended dose of ITK-1 peptides is 3 mg/peptide. The median PFS is 2.3 months

[118]

DSP-7888

Peptide vaccine

NCT02498665

I

Recurrent or advanced AML, MDS, GBM, melanoma, NSCLC, ovarian cancer, pancreatic cancer, sarcoma, or renal cell carcinoma

24

Open label

Dose escalation

DSP-7888 Dosing Emulsion was well tolerated, with no dose-limiting toxicities. Higher WT1-specific cytotoxic lymphocyte induction was noted with intradermal injection. 7 rGBM patients showed robust immune response

[120]

DSP-7888

Peptide vaccine

NCT03149003

III

Recurrent or progressive supratentorial GBM

236

Open label

Double-blind

Two arms

Ongoing

[121]

HLA-A*2402-restricted, modified 9-mer WT1 peptide vaccine

Multipeptide vaccine

–

II

rGBM

21

Open label

Single arm

The overall response rate was 9.5% and the disease control rate was 57.1%, with 2 patients showing partial response, 10 patients under stable disease, and 9 patients under progressive disease. The median PFS was 20.0 weeks, and the 6-month (26-week) PFS rate was 33.3%

[122]

PPV

Multipeptide vaccine

–

III

HLA-A24–positive rGBM

88

Open label

Double-blind

Two arms

The median OS was 8.4 months in PPV group versus 8.0 months in placebo group and no significant difference on median PFS or 1-year survival rate between the two groups

[96, 145]

DCVax-L

DC vaccine

NCT00045968

III

Newly diagnosed GBM and rGBM

331

Open label

Double-blind

Two arms

A group of 64 patients receiving only SOC plus placebo until recurrence, then receiving DCVax-L was defined as placebo arm crossovers. Its median OS was OS in rGBM, which was the secondary endpoint. The median OS was 13.2 months while the external control group was 7.8 months. The 24- months overall survival was 20.7% versus 9.6% and the 30 months survival was 11.1% versus 5.1%

[95, 126]

αDC1 loaded with synthetic peptides + poly-ICLC

Peptide-pulsed DC vaccine

NCT00766753

I/II

Recurrent malignant gliomas

22

Open label

Dose escalation

Single arm

The protocol was well-tolerated. 9 of 22 patients reached a PFS of more than 12 months, with positive immune responses observed in 58% of the patients. One patient demonstrated a sustained complete response

[134]

Autologous DC vaccine pulsed with lysate derived from a GBM stem-like cell line + Bevacizumab

Peptide-pulsed DC vaccine

NCT02010606

I

Newly diagnosed GBM and rGBM

35

Open label

Dose escalation

Cohort expansion

25 patients diagnosed with rGBM were all well tolerated. No severe adverse events occurred. The median OS and PFS were 11.97 months and 3.23 months, and 6-month PFS was 24%, all better than the average

[135]

GSC-DCV

Peptide-pulsed DC vaccine

–

II

Newly diagnosed GBM and rGBM

21

Open label

Dose escalation

Two arms

10 patients with rGBM have a median OS of 10.7 months, and a median PFS of 6.9 month. Subgroup analysis was limited due to the study size

[136]

Gliadel Wafer + tumor lysate-pulsed DC vaccine

Tumor lysate-pulsed DC vaccine

–

I

Primary and recurrent malignant giloma

28

Open label

Dose escalation

Cohort expansion

The protocol was safe and elicited modest immunogenicity. 17 patients with rGBM reached a median OS of 10.9 months and a median PFS of 1.9 months

[138]

WT1-pulsed DC vaccine

Tumor lysate-pulsed DC vaccine

–

I

Recurrent malignant glioma

10

Open label

Dose escalation

The WT1-pulsed DC vaccination therapy proved its safety, immunogenicity, and feasibility. All the enrolled patients finally had a progression in tumor

[139]

Adjuvant DC-based immunotherapy

Tumor lysate-pulsed adjuvant DC vaccine

–

II

Relapsed GBM

56

Open label

Three arms

The median OS and PFS was about 9.6 months and 3 months, with a 2-year OS rate of 14.8%. To make a faster DC vaccination schedule with tumor lysate boosting was likely to improved PFS

[141]

ERC1671 + bevacizumab

Whole tumor vaccine

NCT01903330

II

rGBM

9

Open label

Double-blind

Two arms

The median OS of ERC1671 plus bevacizumab group was 12 months, compared to 7.5 months in the placebo plus bevacizumab group. The increasing maximal CD4 + T-lymphocyte leads to longer survival in ERC1671 group

[143]

ATL-DC

Tumor lysate-pulsed DC vaccine

NCT04201873

I

Surgically accessible rGBM

40

Open label

Dose escalation

Cohort expansion

Ongoing

[144]