Clinical Trial Status Of Investigational Therapy Multikine (Leukocyte Interleukin, Injection)

Multikine (Leukocyte Interleukin, Injection) is the full name of this investigational therapy, which, for simplicity, is referred to in the remainder of this page as Multikine*.

  o The first indication being pursued for Multikine:

Multikine is currently being developed as a potential first-line therapy for advanced primary head and neck cancer. This is a deadly cancer in which there is a recognized unmet medical need.

The recurrence rate following currently available conventional treatment is high for patients diagnosed with advanced primary head and neck cancer and about one out of every two patients will die within three to five years. Currently used therapies (surgery followed by radiation, chemotherapy or radio-chemotherapy) (recommended by the NCCN Clinical Practice Guidelines for Oncology - published by the National Comprehensive Cancer Network) appear not to be able to completely arrest the disease because these treatments are unable to completely remove or kill all of the cancer cells in the advanced primary disease cases. The persistence of these residual cells is thought to be responsible (at least in part) for the cancer's recurrence or metastasis.

In a number of Phase I and II studies, and in the current global pivotal Phase III clinical trial, Multikine investigational therapy was/is being injected five times a week for three weeks around the tumor (peri-tumorally) as well as in the vicinity of the local draining lymph nodes (peri-lymphatically) prior to the patient's tumor being removed surgically and the patient receiving any other therapy because these are the areas in which the cancer is thought to most likely recur and from which metastases would therefore be most likely to develop.

Clinical and histopathology data collected during Phase II clinical trials of this investigational therapy indicate that, in those studies, Multikine therapy appears to have reduced the number of recurrences of tumors in the treated head and neck cancer patients beyond that which would otherwise normally would be expected in this same patient population based on literature reports.  However, no definitive conclusions can be drawn from these preliminary data about the potential efficacy and/or safety profile of this investigational therapy.  Moreover, further research is required, and these results must be confirmed in the well-controlled Phase III clinical trial of this investigational therapy that is currently in progress.

The current underlying understanding of Multikine's apparent mode of action, which presently is based on data from animal (Chirigos et al Immunopharm. and Immunotox. 1995) and human (Timar et al JCO 2005) studies to date, is that it appears to activate the immune system to potentially mount an anti-tumor immune response against the specific individual tumor within each subject treated. This opens up the potential (to be explored in future clinical development) for this investigational therapy to possibly treat other solid tumors in addition to its potential role in head and neck cancer.

Multikine has already preliminarily shown the potential for biological activity (in early clinical trials) in cervical dysplasia / neoplasia (pre-cancer and cancer of the cervix) and prostate cancer.

 

Other potential indications in which development likely would be pursued for Multikine if it is determined by FDA to be safe and effective based upon the entirety of the developmental data including that from the ongoing Phase III clinical study in advanced primary head and neck cancer may include: breast cancer, skin cancer, cervical cancer, melanoma and enhancement of chemotherapy and radiation.  The potential for the possible enhancement of chemotherapy and radiation is a particularly important field to investigate because it may open the potential to reduce the amounts of radiation and possibly chemotherapy given to patients.

 
       
  o Summary of preliminary clinical results from Phase II clinical trials of the investigational therapy Multikine in head and neck cancer patients with advanced primary disease**:  
   
       
  o In the final Phase II clinical study, using the same dosage and treatment regimen as is being used in the Phase III study, head and neck cancer patients with locally advanced primary disease who received the investigational therapy Multikine as first-line investigational therapy followed by surgery and radiotherapy were reported by the clinical investigators to have had a 63.2% overall survival (OS) rate at 3.5 years from surgery. This percentage OS was arrived at as follows: of the 22 subjects enrolled in this final Phase II study, the consent for the survival follow-up portion of the study was received from 19 subjects. One subject did not consent to the follow-up portion of the study. The other 2 subjects did not have squamous cell carcinoma of the oral cavity and were thus not evaluable per the protocol. The overall survival rate of subjects receiving the investigational therapy in this study was compared to the overall survival rate that was calculated based upon a review of 55 clinical trials conducted in the same cancer population (with a total of 7294 patients studied), and reported in the peer reviewed scientific literature between 1987 and 2007. Review of this literature showed an approximate survival rate of 47.5% at 3.5 year from treatment. Therefore, the results of CEL-SCI's final Phase II study were considered to be potentially favorable in terms of overall survival recognizing the limitations of this early-phase study. It should be noted that an earlier investigational therapy Multikine study appears to lend support to the overall survival findings described above -Feinmesser et al Arch Otolaryngol. Surg. 2003. However, no definitive conclusions can be drawn from these data about the potential efficacy or safety profile of this investigational therapy. Moreover, further research is required, and these results must be confirmed in the well-controlled Phase III clinical trial of this investigational therapy that is currently in progress. Subject to completion of that Phase III trial and FDA's review and acceptance of CEL-SCI's entire data set on this investigational therapy, CEL-SCI believes that these early-stage clinical trial results indicate the potential for this investigational therapy to become a treatment for advanced primary head and neck cancer.

The primary clinical endpoint in CEL-SCI's ongoing Phase III clinical trial specify that a 10% improvement in overall survival in the Multikine treatment arm plus the current standard of care (SOC - consisting of surgery + radiotherapy or surgery + radiochemotherapy) over that which can be achieved in the SOC arm alone (in the well-controlled Phase III clinical trial currently ongoing) must be achieved in order to meet the primary endpoint of the Phase III study. Based on what is presently known about the current survival statistics for this population, CEL-SCI believes that achievement of this endpoint should enable CEL-SCI, subject to further consultations with FDA, to move forward, prepare and submit a Biologic License Application to FDA for Multikine.
 
       
 o Data from the Final Phase II study has also shown the following:  
       
  o Reported average of 50% reduction in tumor cells in Phase II trials: The clinical investigators who administered the 3 week Multikine treatment regimen used in Phase II studies reported that, as was determined in a controlled pathology study, Multikine administration appeared to have caused, on average, the disappearance of about half of the cancer cells present at surgery (as determined by histopathology assessing the area of Stroma/Tumor (Mean+/- Standard Error of the Mean of the number of cells counted per filed)) even before the start of standard therapy like radiation and chemotherapy (Timar et al JCO 2005).  
       
  o Reported 12% complete response in the final Phase II trial: The clinical investigators who administered the 3 week Multikine investigational treatment regimen used in the final Phase II study reported that, as was determined in a controlled pathology study, the tumor apparently was no longer present (as determined by histopathology) in approximately 12 % of patients (2 of 17 evaluable by pathology). This determination was made by three pathologists blinded to the study from the surgical specimen after a 3 week treatment with Multikine (Timar et al JCO 2005).  
       
  o Adverse events reported in clinical trials: In Phase I and Phase II clinical trials conducted to date, with the Multikine investigational therapy, adverse events associated with the investigational therapy Multikine administration which have been reported by the clinical investigators included pain at the injection site, local minor bleeding and edema at the injection site, diarrhea, headache, nausea, and constipation.  
       
    The clinical significance of these and other data, to date, from the multiple Multikine clinical trials is not yet known. These preliminary clinical data do suggest the potential to demonstrate a possible improvement in the clinical outcome for patients treated with Multikine. However, no definitive conclusions can be drawn from these data about the safety or efficacy profile of this investigational therapy, and further research is required and the global Phase III study is ongoing in an effort to confirm these results.  
 
     

* Multikine is the trademark that CEL-SCI has registered for this investigational therapy, and this proprietary name is subject to FDA review in connection with our future anticipated regulatory submission for approval.

** Multikine has not been licensed or approved for sale, barter or exchange by the FDA or by any other regulatory agency. Similarly, its safety or efficacy has not been established for any use. Moreover, no definitive conclusions can be drawn from the early-phase, clinical-trials data summarized on this page or elsewhere on this website involving the investigational therapy Multikine (Leukocyte Interleukin, Injection). Further research is required, and early-phase clinical trial results must be confirmed in the well-controlled, Phase III clinical trial of this investigational therapy that is currently in progress.