A Randomized Double-Blind Placebo-Controlled Phase II Trial of Dendritic Cell Vaccine ICT-107 in Newly Diagnosed Patients with Glioblastoma

Treatment scheme

Treatment scheme

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Summary

This study focuses on the effects of an autologous Dendritic Cell vaccine pulsed with six synthetic peptide epitopes for glioblastoma (GBM). The vaccine was well tolerated and increased progression-free survival by 2.2 months while maintaining the quality of life.This is the first vaccine trial in GBM to show a clinical benefit.

Patients characteristics

124 patients were >18 years old with the median age of 59.2 (range, 22.9–81.8) with histologically confirmed GBM and had undergone gross total resection resulting in no residual gadolinium enhancement. Karnofsky performance status (KPS) 70% median KPS was 90 (range, 70–100), HLA-A1+ or HLA-A2+, and adequate bone marrow, liver, and renal function.

Methodology

ICT-107 production involves harvesting monocytes from each subject through plasmapheresis, driving the monocytes to differentiate into DCs, and then activating the new DCs by incubating them with peptides present on GBM stem and tumor cells. Monocyte differentiation is triggered by culturing these cells with recombinant human GM-CSF and IL4, followed by IFNg and bacterial lipopolysaccharide. The resulting DCs are then incubated with 20 mg/mL of each of six preselected synthetic peptides, 9–10 amino acids in length, derived from antigens associated with cancer stem cells in GBM. ICT-107 vaccination consisted of 1mL of pulsed DCs (1.1×107 cells/mL). Control consisted of 1 mL of DCs un-pulsed with antigen (3.6×106 cells/mL).

Treatment

ICT-107 vaccination consisted of 1mL of activated, mature, pulsed DCs (1.1×107 cells/mL). Control consisted of 1 mL of activated, mature, un-pulsed DCs (3.6×106 cells/mL). In the 4-week interval after the rest period, between the completion of radiotherapy and the beginning of adjuvant temozolomide (vaccine induction phase), patients received vaccination once weekly intradermally in the axilla. Patients then began the maintenance phase and received standard adjuvant temozolomide at 150 mg/m2/d x5 days for cycle 1, and then 200 mg/m2/day x5 days on cycles 2 to 12. Additional vaccinations were administered day 21 of cycles 1, 3, 6, 10 and then every 6 months.

Results

Overall, the vaccine was well tolerated. The most frequent adverse events were fatigue, convulsions, and nausea. There was no difference in adverse events between ICT-107 and the control DC group.
Efficacy
At the 67-event trial completion point, the primary efficacy endpoint of OS for the ICT-107 group in the ITT population was 17.0 months (CI: 13.68–20.61) and was not significantly increased compared with the 15.0 months (CI: 12.33–23.05) for the control group. However, the secondary endpoint, PFS, for ICT-107 of 11.2 months (CI: 8.22–13.05) was statistically significantly increased compared with 9.0 months (CI: 5.52– 10.29) for the control group. At 99 events, median OS favored ICT-107 by 1.6 months. PFS, for ICT-107 of 11.4 months was statistically significantly increased compared with the 10.1 months for the control group. Analysis of the tumor specimens showed that while over 90% of patients expressed all the HLA- A2 antigens, only 37.8% of patients expressed the HLA-A1 antigens. For HLA-A2+ patients with MGMT promoter methylation, median PFS for the ICT-107 group was 24.1 months compared with a median PFS of 8.5 months for the control group, while median OS for the ICT-107 group was 33.7 months compared with 23.9 months for the control group. For HLA-A2+ patients with unmethylated MGMT promoter, median PFS for the ICT-107 group was 10.5 months compared with 6.0 months for the control group, while median OS was 15.8 months for the ICT-107 group compared with 11.8 months for the control group. HLA-A1+ patients with unmethylated MGMT promoter treated with ICT-107 had a median OS of 14.3 months compared with 15.1 months for the control group. The HLA-A1+ patients with MGMT methylation treated with ICT-107 had a median OS of 47.6 months compared with 25.8 months for the control group (P 1⁄4 0.049).

Conclusion

In conclusion, PFS was significantly improved in ICT-107– treated patients with maintenance of QoL. Patients in the HLA-A2 subgroup showed increased ICT-107 activity clinically and immunologically.

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Scientific article publishing date : 15/10/2020

Immucura identifier : BSC21_056EN

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