Investigational Therapy Multikine (Leukocyte Interleukin, Injection) Phase III Clinical Trial Design and Status

The Phase III Clinical Trial: Multikine (Leukocyte Interleukin, Injection) has been cleared for a global Phase III trial in advanced primary head and neck cancer. It has received a go-ahead from 24 Regulatory Agencies worldwide including leading regulators in the U.S., Canada and the United Kingdom. Multikine (Leukocyte Interleukin, Injection) is the full name of this investigational therapy, which, for simplicity, it is referred to in the remainder of this page as Multikine*. Multikine has not been licensed or approved 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 this investigational therapy.

Because of Multikine's orphan drug status in the USA, it currently is anticipated that only one pivotal study is expected to be necessary for Multikine's approval. The indication where Multikine is being investigated as a potential treatment in the Multikine Phase III Study is advanced primary, not yet treated, head and neck cancer, which represents a recognized unmet medical need.

In August 2016, CEL-SCI announced that the data available at that time from the Phase 3 clinical study reflected that the accumulation of deaths in the study was lower than that which was anticipated based on reported literature at the Phase III study's inception. If the number of deaths continued to be accumulated at the rate at that time, it had been determined that it would take longer than originally planned to complete the study. To minimize this eventuality, CEL-SCI decided it would be necessary to enroll additional patients. As required by law and in order to be able to implement the plan, CEL-SCI submitted an amendment to the existing Phase III protocol for our head and neck cancer study to the FDA and multiple regulatory agencies in the countries abroad where the Phase III study is being conducted to allow for this expansion in patient enrollment. Subsequently, on September 26, 2016, the FDA had placed the Phase III clinical trial in advanced primary head and neck cancer on clinical hold.

In April 2017, CEL-SCI announced that in light of new information CEL-SCI has decided to withdraw the study protocol amendment for additional patients that was submitted to the FDA and other regulatory agencies in the summer of 2016. It is now possible that CEL-SCI may not need to add more patients to the study or that only a smaller number of patients need to be added to the study to complete it in a reasonable period of time. Should additional patients be needed, CEL-SCI will submit a future study amendment to the FDA and other regulatory agencies to seek their clearance to proceed.

On August 14, 2017, CEL-SCI announced that it has received a letter from the FDA stating that the clinical hold that had been imposed on the Company's Phase III cancer study with Multikine has been removed and that all clinical trial activities under this Investigational New Drug application, or IND, may resume.

Nine hundred twenty-eight (928) newly diagnosed (not yet treated) head and neck cancer patients have been enrolled in this Phase III cancer study and all the patients who have completed treatment continue to be followed for protocol-specific outcomes in accordance with the Study Protocol. The study's primary endpoint is a 10% increase in overall survival for patients treated with the Multikine treatment regimen plus Standard of Care (SOC) versus those who receive SOC only. The determination if the study's primary end point has been met will occur when there are a total of 298 deaths in those two groups. Current SOC for this indication is surgery, followed by radiation therapy alone or followed by concurrent radio-chemotherapy (as defined by the National Comprehensive Cancer Network, or NCCN, guidelines).

In 2013, CEL-SCI was faced with a major challenge. We were forced to transfer the management of the Phase III trial for Multikine in the treatment of head and neck cancer to two new Clinical Research organizations (CROs). In April 2013, CEL-SCI had to dismiss the prior CRO that had this responsibility because, among other things, they did not achieve the rate of patient enrollment in our study assumed by our contract, and they had a high internal rate of turnover among their personnel which negatively affected the conduct of our Phase III trial.

Our ongoing Phase 3 trial is testing the hypothesis that Multikine treatment, administered prior to such SOC treatment regimen, will extend overall survival, enhance the local/regional control of the disease and reduce the rate of disease progression in patients with squamous cell carcinoma of the head and neck, or SCCHN. SCCHN is the most common type of head and neck cancer.

This study is also thought to be the first Phase III study in the world in which immunotherapy is given to patients first meaning it is given after diagnosis and before any conventional treatment for cancer. It seems logical to us that boosting an intact immune system should be more helpful to patients than trying to boost a significantly weakened immune system after radiation and chemotherapy. Below is a general overview of the current Phase III clinical trial.

Study Summary: A Pivotal Phase III, Open-label, Randomized, Controlled Multi-center Global Study of the Effects of Multikine Plus Standard of Care (Surgery + Radiotherapy or Surgery + Concurrent Chemoradiotherapy) in Subjects with Advanced Primary Squamous Cell Carcinoma of the Oral Cavity and Soft Palate Versus Standard of Care Only.

Objectives: As set forth in the study protocol, the primary objective of this Phase III trial is to evaluate the efficacy of peri-tumoral and peri-lymphatic injection of the investigational Multikine therapy given prior to SOC. This will be primarily evaluated based upon measurements of overall survival. The secondary objectives are to evaluate the effects of the investigational Multikine therapy on the cumulative incidence of local-regional control, progression-free survival, tumor histopathology, and quality of life, while also seeking to confirm Multikine safety. Tumor response is a tertiary outcome in this immunotherapy study.

Number of Subjects: 880. Enrolled: 928

Clinical Centers: approximately 100 globally distributed; North America, Europe, Asia


* 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 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.