View source for ICT-107

{{TreatmentInfo
|drug_name=ICT-107 (Tumor-associated Antigen Vaccine)
|FDA_approval=Still in clinical trials; not yet FDA-approved
|used_for=Newly diagnosed and recurrent Glioblastoma Multiforme (GBM)
|clinical_trial_phase=Phase III
|common_side_effects=Reported side effects are minimal, including potential site reactions and flu-like symptoms. Few serious adverse events related to the vaccine have been reported.
|OS_without=Median overall survival for GBM typically ranges around 16 months with standard treatment.
|OS_with=Varies; earlier phases showed median overall survival up to 38 months in phase I trial participants.
|PFS_without=Standard treatments offer a median progression-free survival of about 6.9 months.
|PFS_with=Phase II trial showed a significant improvement in PFS, particularly for HLA-A2 positive patients with methylated MGMT, showing a median PFS of 24.1 months vs. 8.5 months in the control group.
|usefulness_rating=4
|usefulness_explanation=ICT-107 has demonstrated potential in extending progression-free and overall survival in GBM patients, especially in specific subgroups. Its ability to target multiple tumor-associated antigens may offer a broader immunogenic response.
|toxicity_level=2
|toxicity_explanation=The vaccine has shown a benign safety profile with minimal severe adverse effects, making it a potentially safer alternative or complement to existing GBM treatments.
|book_text=One disadvantage of the DCVax approach is that it requires that brain tissue be extracted
from individual patients in order to make the vaccine. An alternative approach has been
used by Dr. Black’s team at Cedars Sinai. Dendritic cells are still drawn from the
peripheral blood of individual patients, but instead of tumor tissue lysate being mixed
with those cells, a collection of six proteins typical of of GBMs is mixed with the

dendritic cells, creating an immune response to those antigens, with the mixture then
returned to the patient via vaccinations. In a phase I trial (158), 20 GBM patients (17
newly diagnosed, 3 with recurrent tumors) received three vaccinations two weeks apart.
Median PFS was 16.9 months, and median overall survival was 38 months. At the time of
the clinical trial report, six of the patients had shown no sign of tumor recurrence. A later
follow-up was reported in a Press release from ImmunoCellular Therapeutics (159), the
biotech company sponsoring the vaccine (now called ICT-107). Survival rate at three
years was 55%, with 38% of patients showing no evidence of recurrence, The most

recent update of the clinical trial (160), presented at the 2013 meeting of the World
Federation of Neuro-oncology, reported that 7 of the original 16 patients in the trial were
still alive, with survivals ranging from 60 to 83 months. One additional patient who was
still tumor free after five years died from leukemia.

Currently ongoing is a randomized phase II trial, the interim results of which have
recently reported by ImmunoCellular Therapeutics (161). Despite the impressive results
described above, there was no statistically significant difference in median survival
between the vaccine group and those treated with a placebo, although there was a
numerical 2-3 month advantage for the vaccine group. However there was a similar
difference in progression-free survival, which was statistically significant. The company
emphasized that the results were preliminary and that they expected the difference in
progression-free survival to translate into differences in overall survival with longer
follow-up. However, the results also suggest that median survival and percentage of
long-term survivors may be only weakly correlated due to the possibility that only a
minority of patients benefit from the treatment, but those who do benefit a great deal.

Updated data from the phase II ICT-107 trial were presented on June 1, 2014 at the
annual ASCO meeting (309). An important conclusion to be drawn from the new data is
that mainly patients positive for HLA-A2 (a variant of the Human Leukocyte Antigen-A
gene) seem to derive significant benefit from the vaccine. HLA are antigen-presenting
proteins found at the cell surface. HLA-A2 is the most common variant in North America
and Europe according to the press release and this group comprised 62% of patients
randomized in this trial. The updated results are presented only for HLA-A2 positive
patients, with results further subgrouped according to MGMT methylation status.
Survival results in this trial are measured from the time of randomization after
chemoradiation, and average time from initial surgery to randomization was 83 days (2.7
months).

For HLA-A2 positive patients with unmethylated MGMT, the ICT-107-vaccinated group
had a median 4-month survival advantage compared with the placebo-vaccinated group.
The ICT-107 group also had a median 4.5 month advantage in progression-free survival.
These advantages in the vaccine-treated group did not reach statistical significance,
though that is perhaps due to the small numbers of patients within these subgroups. 21%
of ICT-107 treated patients were still alive at the time of the analysis, compared with only
7% of the placebo-treated patients.

Median survival has not yet been reached in the HLA-A2 positive, MGMT methylated
group, though in this subgroup, ICT-107 treatment led to a dramatic and statistically
significant increase in median progression-free survival: 24.1 months versus 8.5 months
in the placebo-treated group. It is likely that this huge improvement in median
progression-free survival in this subgroup will translate into significant median overall
survival improvement.

Sadly, in June 2017, Immunocellular Therapeutics announced that their phase 3 ICT-107
trial was suspending recruitment due to insufficient funding. In the press release it was
stated the company was looking for a partner for collaboration or acquisition of its
ICT-107 program, and they were also taking steps to ensure the continued follow up of
patients already being treated in the trial.


|links=https://www.frontiersin.org/articles/10.3389/fonc.2020.00762/full, https://tcr.amegroups.org/article/view/4305/5159, https://clinicaltrials.gov/ct2/show/NCT02546102
recent_text= While earlier trials indicated significant benefits in survival and progression-free survival, particularly for patients with certain biomarkers, recent reflections and analyses suggest a more complex picture. These findings emphasize the need for further research to understand the vaccine's full potential and its place in GBM treatment strategies.

The critical insights into the ICT-107 vaccine's efficacy, especially concerning patient-specific factors like HLA-A2 status and MGMT methylation status, underscore the importance of personalized approaches in cancer immunotherapy. Despite the challenges, including funding issues that have impacted the phase III trial, the continued follow-up of patients and the exploration of ICT-107 in combination with other treatments offer hope for advancements in GBM therapy (Frontiers) 
|treatment_category=Tumor-associated antigen vaccines
}}