CEL-SCI Corporation released results from its 9.5 year pivotal Phase 3 study for its immunotherapy Multikine® (Leukocyte Interleukin, Injection)* in the treatment of advanced (stages III and IV) primary (previously untreated) squamous cell carcinoma of the head and neck (SCCHN).
In the intent to treat (ITT) advanced primary SCCHN patients the study showed a statistically significant (p=0.0236, HR=0.68) overall survival benefit of 14.1% with overall survival (OS) of 62.7% at 5 years for the group of patients receiving the Multikine treatment regimen followed by surgery and radiotherapy therapy, but not chemotherapy, as part of their standard of care (SOC) treatment. The OS benefit increased over time. This group represents about 155,000 patients worldwide, or about 40% of all advanced primary head and neck cancer cases annually. Patients treated with the same Multikine treatment regimen prior to surgery and radiotherapy, but who also received chemotherapy, did not exhibit this survival advantage. The chemotherapy, cisplatin, was given intravenously and may have negated the survival benefit imparted by Multikine immunotherapy in these patients.
This global trial enrolled 928 stage III and IVa patients through 78 sites on 3 continents. The ITT population comprised of 923 patients, as 5 randomized patients were never treated. The two main comparator arms of the study were: the Multikine treatment regimen (Multikine plus CIZ: cyclophosphamide; indomethacin; zinc-multivitamins) plus SOC vs. SOC alone. In each of these comparator arms, patients were determined by pathology following surgery to receive radiotherapy only or concurrent radio-chemotherapy. These treatments were prescribed by the protocol and are based on the NCCN (National Comprehensive Cancer Network) Guidelines for the treatment of SCCHN patients. The data were analyzed per the protocol and the Statistical Analysis Plan.
Results for the patients who did not receive chemotherapy treatment as part of their SOC are listed below. This is the group for which CEL-SCI plans to seek FDA approval:
1) Patients treated with the Multikine treatment regimen plus SOC vs. SOC alone had an overall survival benefit of 14.1% at 5 years which exceeded the pre-defined 10% overall survival benefit set out for the study population as a whole. This result was statistically significant (ITT; p =0.0236, HR=0.68) with a robust and durable duration effect exceeding 5 years.
2) The corresponding overall survival at 3 years and 5 years for each study treatment group was as follows: Multikine treatment regimen (Multikine plus CIZ: cyclophosphamide; indomethacin, zinc-multivitamins) plus SOC was 72.4% at 3 years, 62.7% at 5 years; Multikine (no CIZ) plus SOC was 78.8% at 3 years, 55.5% at 5 years. SOC alone was 67.5% at 3 years, 48.6% at 5 years. The primary survival comparison was pre-defined only between the first and last groups.
3) The OS advantage increased over time and was evident from the inception of the study participation for this group of patients through the end of the follow up period with a median follow up time greater than 7 years for those still alive.
4) No safety issues for Multikine were found during or as a result of its administration, including no late effects, in the overall treated patient population.
When the complete study population to which the Multikine treatment regimen was administered (i.e., the combined lower risk (no chemotherapy) and higher risk (with chemotherapy added)) was compared to control, the study did not achieve its primary endpoint of a 10% improvement in overall survival. However, the OS benefit of 14.1% at 5 years for the lower risk subgroup (no chemotherapy) exceeded the 10% OS benefit set out for the study population as a whole. In addition, as the OS results for the lower risk of recurrence patients (no chemotherapy) are significant (two-sided p=0.0236, HR=0.68) and the effect is robust, durable and increasing over time, CEL-SCI plans to seek FDA approval for Multikine cancer immunotherapy in this underserved patient population. This indication represents a dire unmet medical need with the last FDA approval being many decades ago. CEL-SCI has Orphan Drug designation from the FDA for the neoadjuvant therapy in patients with squamous cell carcinoma of the head and neck – the patient population treated in this Phase 3 study.
The analysis of this separate group is expected to meet regulatory requirements for FDA submission based on the protocol and Statistical Analysis Plan, which were prospectively concluded before database lock and unblinding.
Geert Kersten, Chief Executive Officer of CEL-SCI remarked, “Multikine demonstrated a significant survival benefit in the group whose standard of care did not include chemotherapy and a favorable safety profile across the entire patient population. Based on this landmark study data, we intend to seek FDA approval for what could become the first treatment in newly diagnosed advanced primary head and neck cancer in many decades. If approved, Multikine would address the needs of approximately 155,000 patients diagnosed annually worldwide who are currently slated for surgery plus radiotherapy and would significantly increase their chances of overall survival. Our aim with Multikine was to develop a treatment that will extend survival, and clearly this has been achieved in this patient population. In addition, we wanted to develop a treatment that does not add toxicity and does not make other cancer treatments more difficult to bear. We appear to have achieved this goal as well. We are grateful to all the patients and their families who volunteered to participate in the world’s largest and most rigorous Phase 3 study in advanced primary head and neck cancer. We are confident that the robust overall survival benefit shown in this pivotal study along with the safety profile of Multikine clearly demonstrates the benefit of neoadjuvant immunotherapy in this patient population and may lead to a new way to treat advanced primary head and neck cancer.”
Dr. Eyal Talor, Chief Scientific Officer of CEL-SCI and the developer of Multikine commented, “These data, combined with what we know of Multikine’s mechanism of action, demonstrate Multikine’s potential to impart long term overall survival advantage and a beneficial effect on the anti-tumor immune response in patients who have not been treated with chemotherapy (cisplatin) which is known to be highly toxic. In patients not indicated to receive chemotherapy as part of their standard of care, treatment with Multikine neoadjuvant regimen demonstrated a statistically significant, robust and durable overall survival benefit. The data possibly indicate that the Multikine treatment regimen is capable of altering the course of disease in this population. Perhaps most impressive in the Multikine treated group not receiving chemotherapy was the fact that the overall survival benefit imparted by Multikine increased over time as compared to overall survival in control, suggesting that the Multikine immunotherapy neoadjuvant treatment stands to add great benefit to the intent to cure – current standard of care.”