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

The end game is near: The final stages of clinical trials: 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 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, 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. Advanced primary, not yet treated, head and neck cancer represents a recognized unmet medical need.

On August 31, 2016, CEL-SCI announced that the currently available data from the 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 3 Study's inception. If the number of deaths continued to be accumulated at the current rate, 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 up to 1,273 patients to have 1,146 evaluable patients. With this increased patient enrollment, CEL-SCI expected a corresponding increase in the number of deaths, and, if this plan were implemented, the study could be completed in a more timely manner. As required by law and in order to be able to implement the plan, CEL-SCI submitted an amendment to the existing Phase 3 protocol for its head and neck cancer study to multiple regulatory agencies in the countries abroad where the Phase 3 study is being conducted as well as to the FDA to allow for this expansion in patient enrolment. The protocol amendment and the Phase 3 study were put on Partial Clinical Hold by the US FDA.

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.

On September 26, 2016, CEL-SCI received verbal notice from the FDA that the Phase 3 clinical trial has been placed on clinical hold. On October 21, 2016, CEL-SCI issued a press release stating that, "following up on our press release issued on September 26, 2016, we have received the Partial Clinical Hold letter from the FDA. CEL-SCI is working on a response to the FDA and will work diligently with the FDA to seek to have the partial clinical hold lifted."

The current standard of care (SOC) treatment regimen for advanced primary head and neck cancer patients consists of surgical resection of the tumor and involved lymph nodes, followed by either radiotherapy alone or radiotherapy and concurrent chemotherapy as defined by the National Comprehensive Cancer Network, or NCCN guidelines. Our ongoing Phase 3 trial that is on Partial Clinical Hold by the US FDA 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.

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 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. CEL-SCI submitted an amendment to the existing Phase III protocol for its head and neck cancer study to multiple regulatory agencies in the countries abroad where the Phase 3 study is being conducted as well as to the FDA to allow for the expansion in patient enrolment to 1,273.

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 on Partial Clinical Hold by the US FDA.