Updating ImmunoCellular ICT-107 trial data in patients with newly diagnosed GBM presented at ASCO 2014

Updating ImmunoCellular ICT-107 trial data in patients with newly diagnosed GBM presented at ASCO 2014 -

ImmunoCellular Therapeutics, Ltd. ( "ImmunoCellular") (NYSE MKT: IMUC) announced that the efficacy and safety of updated data from the Phase II trial of dendritic cell-based immunotherapeutic vaccine ICT-107 in newly diagnosed patients with glioblastoma (GBM) were presented in 2014 to the American Society of clinical oncology (ASCO) annual meeting in Chicago.

When overall survival (OS) and progression-free survival (PFS) were evaluated in pre-specified patient subgroups, favorable results to treatment with ICT-107 Control in HLA-A2 patients within each of the two major subgroups MGMT (unmethylated and methylated). Although subgroups were small, and not powered to show statistical significance, numerical advantages for ICT-107 treated patients were found to be significant and clinically meaningful.

HLA (human leukocyte antigens) are proteins with the cell surface antigen. These molecules on dendritic cells present antigens and tumor-associated T cells to induce the immune response to vaccine ICT 107. HLA-A2 was one of the two HLA types which have been treated in the Phase II. Of the two types, HLA-A2 is twice as common in the population HLA-A1 and HLA type is most common in North America and the European Union.

In the per protocol analysis (PP) HLA-A2 patient data with MGMT unmethylated

• The control and treated Median OS times were 11.8 and 15 , 8 months, respectively, indicating an increase in the digital survival of 4 months or 33% for patients treated.
• The median PFS time for the control and treated patients were 6.0 and 10.5 months, respectively, indicating an increase of about digital PFS 4.5 months or 75% for treated patients.
• There were also signs of a survival advantage long-term potential for ICT-107-treated patients, with 21% of patients treated still alive, compared with only 7% of controls.

In the PP analysis of data from HLA-A2 patients with methylated MGMT:

• The control and treated groups had not yet reached median survival time that time data analysis, with the majority of patients still alive (65% of treated compared to control 57% of patients);
• However, the median PFS time for the control and treated patients were 8.5 and 24.1 months, respectively, indicating an increase of about significant PFS of 15.6 months, or 184% statistically for treated patients.

data updates to ICT-107 Phase II trial were presented in an oral session by Patrick Y. Wen, MD, director of the Center for Neuro-Oncology in Dana Farber cancer Institute and Professor of neurology at Harvard Medical School, and lead investigator of the trial. The presentation was entitled "A randomized, double-blind, placebo-controlled phase 2 against dendritic cell (DC) vaccination with ICT-107 in newly diagnosed glioblastoma multiforme (GBM) patients."

"We believe that the Phase II trial of maturation data demonstrate a convincing rationale for Phase III development of ICT-107 in patients with newly diagnosed glioblastoma," said the Dr Wen. "Standard-of-care chemotherapy, temozolomide, has little or no therapeutic benefit for newly diagnosed GBM patients with MGMT unmethylated, which is the majority of patients. ICT-107 has shown the potential to significantly extend both OS and PFS without significant side effects in this patient population has the worst prognosis for survival. moreover, the first elements of a potential long-term survival "tail", even in this small trial Phase II is promising and indicative of what we expect to see in an immunotherapeutic agent very active. as MGMT methylated group is followed further, I am optimistic that the already very strong increase in PFS for patients treated in ultimately can lead a survival advantage. "

" analyzes the pre-specified subgroup in our Phase II trial indicate the potential value of an approach to the target population in the future that the proof of therapeutic benefit in HLA-A2 positive patients present a case to the selection of patients for the population to be studied in phase III clinical trials, "said Andrew Gengos, CEO of ImmunoCellular. "HLA-A2 patients represent the majority of the population overall GBM patients in the US and Europe. These new results provide a solid basis for conducting recording discussions with US and European regulatory authorities, we intend to start in the coming months. We want to express our gratitude to patients, researchers and clinical teams who participated in the-107 ICT Phase II trial. We look forward to potentially advancing this vaccine against the promising cancer to the market. "

additional update ICT-107 Phase II results

as reported in December 2013, and the updated data presented at ASCO, OS for the ITT and PP populations showed a digital, but no statistics, treatment benefit. PFS for the ITT and PP populations showed a profit of statistical processing.

• The presentation of the 124 patients randomized, phase II controlled trial was based on approximately 17.6 and 16.2 months of median follow-up of ICT-107 patients and control , respectively. In April, a total of 79 events (patient deaths) were recorded, representing an additional 12 events since the first row of data from the Phase II trial were reported in December 2013. 30 active patients and 15 witnesses were alive for a total of 45 patients available for additional monitoring.
• Median OS in the ITT updated results was 18.3 months for ICT-107 and 16.7 months for the control, which is a numerical advantage for the group of 1.6 month treatment.
• median PFS in the ITT updated results was 11.2 months for ICT-107 and 9.0 months for the control, which is a statistically significant benefit for the group of 2.2 months of treatment.
• Both OS and PFS median results in ICT-107 Phase II trial were measured from the time of randomization (ie, early vaccination after surgery and standard chemoradiation for care). In historical studies of patients with newly diagnosed GBM (eg Stupp, et al.), OS and PFS measures have probably been evaluated from the time of surgery. In test ICT-107 Phase II, there was an average of about 83 days of surgery to randomization.
• Vaccine activity was assessed by measurement of key indicators of dendritic cells to mature cells and activation and their correlation with survival time. Two key indicators of IL-12 and the expression of HLA-DR were predictive of survival in all patients treated in the results announced in December. In the updated results, IL-12 secretion and the expression of HLA-DR were again correlated with survival time treated patients in the Cox Proportional hazards models, with p-values ​​of 0.048 and 0.006 , respectively.

Feedback additional test parameters

data on quality of life, as well as certain immunological parameters, including the activity of the vaccine and the expression of the antigen, were also presented.

• quality of life was evaluated in the Phase II trial with both using the FACT-BR assessment tool and through monitoring of patient performance levels function Karnofsky performance status (KPS). For FACT-BR, there was no difference in the overall evaluation between treated and control groups of the base by the progress. Because the treated patients had a PFS statistically, it means they have more months of the same quality of life compared to the control group to progression. Patients also maintained an increase of KPS immediately before vaccination began with 19 weeks. The rank test p-signed value was less than 0.05 for each of the four evaluations KPS between these time points.
• The patients were evaluated for vaccine response at baseline (pre-vaccination) and three time points during the immunization. The response was evaluated by ELISPOT, and the patients were classified as responders if their T cells (from blood samples) have responded to one of the six antigens used for challenging samples. 27% of patients were responders against 15% of controls. In the HLA-A2 subgroup, 33% of patients were responders against 15% of controls.
• Primary tumors of patients were evaluated for the expression of six vaccine antigens by qPCR. Among all patients, 75% expressed at least one antigen and 51% expressed at least four antigens. In the control group, 93% expressed at least one antigen and 65% expressed at least four antigens. In the HLA-A2 subgroup patients treated, 94% expressed at least one antigen and 85% expressed all four HLA-A2 antigens. For control patients, 100% expressed at least one antigen and 97% expressed the four HLA-A2 antigens.

Next steps for ICT-107 program

ImmunoCellular plans to consult further with the International Neuro-oncology community, and to keep regulatory discussions in the United States and EU on ICT-107.

The Company is finalizing the design of the Phase III protocol in preparation for discussions with the FDA and the European Medicines Agency, or EMA. Plans are underway to seek an end of Phase II meeting with the FDA, scheduled to take place during the summer. After typical European protocol for the meeting with the EMA, ImmunoCellular asked board meetings at the national level in Germany, the UK and the Netherlands to discuss ICT-107. These meetings should take place later in June. In the third or fourth quarter of 2014, the company plans to seek advice from the EMA on the approval process for ICT-107.

ImmunoCellular also plans to continue to monitor patients in the phase II trial and to update the analysis of data at scientific meetings to come, such as potentially meeting the Neuro-Oncology Society ( SNO) in November.