STING (Study of Immunotherapy in Newly Diagnosed Glioblastoma): A Phase III randomized double-blind, controlled study of ICT-107 with maintenance temozolomide (TMZ) in newly diagnosed glioblastoma following resection and concomitant TMZ chemoradiotherapy

ICT-107 is a DC therapy designed to induce immunity capable of rejecting an
established tumor, especially if the tumor is in a minimal residual state such
as after complete surgical resection. The DCs that are contained within ICT-107
secrete their own IL-12, thereby providing their own *adjuvant.* In addition it
has been shown that the antigens targeted by the peptides are expressed on
glioblastoma cells and cancer stem cells. By targeting multiple antigens with
MHC Class I peptides that induce the T-cell immune response most associated
with clinical benefit, ICT-107 can prevent the emergence of antigen negative
escape variants. Targeting cancer stem cells may delay or prevent tumor
recurrence.
It is believed that this clinical study will present minimal risk to
participants. This assessment is based on:
* Results from the Phase I and Phase II studies conducted with ICT-107 have
shown a good safety profile combined with clinical potential. This suggests the
potential for therapeutic efficacy of ICT-107 with minimal risk, justifying
additional clinical studies in this population, which has a clear and unmet
medical need.
* Safety data from ~50 clinical trials performed with various peptide pulsed DC
from 1998 to the present reported in the literature with only Grade 1 and Grade
2 AEs.
* This Phase III study plans a schedule of frequent monitoring and laboratory
testing to capture early signs of AEs or intolerability.
* The convening of an independent DMC for this Phase III trial.

Primary Objective
* To determine the OS of subjects treated with ICT-107 and standard of care (RT
and TMZ) vs. placebo control and standard of care (RT and TMZ) :
Secondary Objectives
* To determine the OS of subjects with unmethylated MGMT tumors treated with
ICT-107 and standard of care vs. control and standard of care :
* To determine the OS of subjects with methylated MGMT tumors treated with
ICT-107 and standard of care vs. control and standard of care.
* To evaluate progression-free survival (PFS) of subjects treated with ICT-107
and standard of care vs. control and standard of care
* To determine the overall safety of ICT-107 vs. control

This is a double blind Phase III study where eligible subjects are randomized
into two treatment arms following the SOC primary treatment with
chemoradiation: Arm 1 will receive ICT-107 in combination with the standard of
care, temozolomide (TMZ), Arm 2 will receive TMZ with a blinded control
consisting of autologous monocyte-enriched peripheral blood mononuclear cells
(PBMC).

Study Therapy Regimen:
All Administrations: Intradermally in axilla
Induction Phase: Induction will consist of administration of subject-specific
study therapy once a week for 4 weeks.
Maintenance Phase: Maintenance will consist of administration of
subject-specific therapy monthly for the 11 months after induction and once
every 6 months thereafter until depletion of supply or confirmation of
progressive disease (PD). Subject-specific study therapy and TMZ will be
administered two weeks apart during Maintenance Cycle 1 to Maintenance Cycle 6.
TMZ will be given Days 1-5 ± 2 days on a 28-day cycle. Study therapy will be
given on Day 21 ± 2 days.
Standard of Care (SOC) Regimen:
Radiotherapy Regimen
Post Surgery SOC: 5 days per week, every week during the Post-Surgery Standard
of Care Treatment Phase (Week -7 to Week -2) :
Administration: As per SOC and institutional procedures
Dose: 60 Gy in 30 fractions
TMZ Regimen
Post Surgery SOC: SOC, daily for 42 days (Week -7 to Week -2) :
Maintenance: SOC; 5 days per month for 6 months (Day 1 - Day 5 from Cycle 1 -
Cycle 6)
Administration: As per institutional procedures; hard capsules provided as
commercially available
Dose: Induction: 75 mg/m2/day
Maintenance Cycle 1: 150 mg/m2/day
Maintenance Cycle 2 to Cycle 6: 200 mg/m2/day

There may be side effects associated with the study therapy and procedures for
the study. Some potential side effects
are: fatigue, convulsions and nausea. Other potential side effects seen in the
previous study include headache,
muscle weakness, changes in blood cell counts, infection, decreased appetite,
difficulty sleeping, and skin rash.
With the injection, there is the chance of an allergic reaction. With the
Immune System Testing there may be pain or
swelling. The potential side effects of the Td vaccine include mild pain,
redness, or swelling where the injection is
given, mild fever, headache, and feeling tired. Rarely, a high fever (over
102°F or 39°C), severe pain, redness, and
swelling where the injection was given or fainting can occur. Severe allergic
reaction can also occur, but it is very rare.
For the routine laboratory tests- blood drawing does not usually have any
risks, but in rare cases it can cause pain,
bleeding, burning, dizziness, fainting, or a bruise or an infection at the site
where the needle was inserted to take the
blood
Apheresis- The patient may experience temporary discomfort, including pain,
irritation, swelling, or bruising at the
place where the needle was inserted into the vein to collect the blood.
Apheresis can also occasionally cause
nausea, vomiting, fainting, seizures, blood loss, infection, skin rash,
flushing, hives, numbness and tingling, swelling
of feet and ankles, or cramps in hands or feet. Patient may also feel cold
during the procedure.
Magnetic Resonance Imaging (MRI)- can be loud and is carried out in a small
space so may not be suitable for
subjects with claustrophobia.
Radiation and chemotherapy
During this study patient will receive standard treatment with radiation
therapy and chemotherapy (temozolomide).
There may be risks associated with these treatments.
Immune System Testing
For the immune system test, the study doctor or nurse will inject the tetanus
diphtheria (Td) vaccine just under the
skin. The potential side effects of the Td vaccine include mild pain, redness,
or swelling where the injection is given,
mild fever, headache, and feeling tired. Rarely, a high fever (over 102°F or
39°C), severe pain, redness, and swelling
where the injection was given, or fainting can occur. Severe allergic reaction
can also occur, but it is very rare.
Risks can be minimized for injection reactions by pre-medicating with
anti-histamine. MRI patient can wear ear
defenders.
The clinical experience to date provides strong evidence for potential clinical
benefit with an acceptable risk profile. Taken together, available information
suggests that the benefit/risk ratio for ICT-107 therapy is acceptable for
further development.