CEL-SCI’s Multikine® Immunotherapy Produces Significant 14.1% 5-Year Survival Benefit (62.7% Vs 48.6%) in the Group Receiving Surgery Plus Radiotherapy in a Landmark Head and Neck Cancer Phase 3 Study

Rhea-AI Summary

CEL-SCI Corporation (NYSE American: CVM) announced results from a pivotal 9.5-year Phase 3 study of its immunotherapy Multikine for advanced primary squamous cell carcinoma of the head and neck. The treatment demonstrated a statistically significant 14.1% overall survival benefit (OS) at 5 years (62.7%) for patients not receiving chemotherapy. The study enrolled 928 patients across 78 sites, showing no safety issues. Although the overall trial did not meet the primary endpoint, the results for the chemotherapy-free subgroup warrant an FDA approval request, highlighting an unmet medical need for around 155,000 patients annually.

Positive

• 14.1% overall survival benefit at 5 years (62.7%) for the Multikine treatment group not receiving chemotherapy, exceeding the predefined 10% threshold.
• No safety issues reported during the trial.
• Plans to seek FDA approval for Multikine based on significant survival advantage in the lower risk subgroup.

Negative

• Overall trial did not meet its primary endpoint of a 10% improvement in overall survival when including patients who received chemotherapy.
• Potential for challenges in regulatory approval due to mixed results across the entire study population.

CEL-SCI Corporation (NYSE American: CVM) today announced 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.”

About Multikine

Multikine (Leukocyte Interleukin, Injection) is an investigational cancer immunotherapy that is known to contain 14 natural human cytokines, the body’s immune system regulators including interleukins, interferons, chemokines, and colony stimulating factors which are elements of the body’s natural mix of defenses against cancer and other diseases. A patented, mass-produced, off the shelf and ready to use non-autologous biological product, Multikine is manufactured using a proprietary process following Good Manufacturing Practice (GMP) requirements from Source Leukocytes, an FDA licensed product, at CEL-SCI’s manufacturing facility near Baltimore, Maryland.

About Head and Neck Cancer

Approximately 650,000 new cases of head and neck cancer are diagnosed each year globally, of which approximately 60,000 are in the U.S. and 105,000 in Europe. Head and neck cancer represents 6% of all cancers and leads to 300,000 deaths annually. Advanced (stages III and IV) primary (previously untreated) squamous cell carcinoma of the head and neck represent approximately 386,000 cases per year and about 40% of these, or approximately 155,000, are patients diagnosed at lower risk for recurrence and therefore are given only radiotherapy following surgery as part of their standard of care, and no chemotherapy.

About CEL-SCI Corporation

CEL-SCI believes that boosting a patient’s immune system while it is still intact should provide the greatest possible impact on survival. Therefore, in the Phase 3 study CEL-SCI treated patients who are newly diagnosed with advanced primary squamous cell carcinoma of the head and neck with the investigational product Multikine first, BEFORE they received surgery and radiotherapy or surgery plus concurrent radiotherapy and chemotherapy (the current standard of care for these patients). This approach is unique. Most other cancer immunotherapies are administered only after conventional therapies have been tried and/or failed. Multikine (Leukocyte Interleukin, Injection), received Orphan Drug designation from the FDA for neoadjuvant therapy in patients with squamous cell carcinoma (cancer) of the head and neck. CEL-SCI believes that this Phase 3 study is the largest Phase 3 study in the world for the treatment of advanced primary head and neck cancer.

Multikine is designed to help the immune system “see” the tumor at a time when the immune system is still relatively intact and thereby thought to be better able to mount an attack on the tumor. The Phase 3 study was started in early 2011 and was fully enrolled with 928 patients in September 2016. To prove an overall survival benefit, the study required CEL-SCI to wait until at least 298 (deaths) events had occurred among the two main comparator groups. This study milestone occurred in late April 2020 and database lock occurred in December 2020.

The Company’s LEAPS technology is being developed for rheumatoid arthritis and as a potential treatment for COVID-19 infection. The Company has operations in Vienna, Virginia, and near/in Baltimore, Maryland.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. When used in this press release, the words "intends," "believes," "anticipated," "plans" and "expects," and similar expressions, are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Such statements include, but are not limited to, statements about the terms, expected proceeds, use of proceeds and closing of the offering. Factors that could cause or contribute to such differences include, an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI's filings with the Securities and Exchange Commission, including but not limited to its report on Form 10-K for the year ended September 30, 2020. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.

* Multikine (Leukocyte Interleukin, Injection) is the trademark that CEL-SCI has registered for this investigational therapy, and this proprietary name is subject to FDA review in connection with the Company's future anticipated regulatory submission for approval. Multikine has not been licensed or approved for sale, barter or exchange by the FDA or any other regulatory agency. Similarly, its safety or efficacy has not been established for any use.

View source version on businesswire.com: https://www.businesswire.com/news/home/20210628005472/en/

FAQ

What were the key findings from CEL-SCI's Phase 3 study of Multikine (CVM)?

The key findings showed a 14.1% overall survival benefit at 5 years for patients treated with Multikine without chemotherapy, achieving a statistically significant result (p=0.0236).

How many patients were enrolled in the CEL-SCI Phase 3 Multikine trial?

The trial enrolled 928 patients across 78 sites on three continents.

What is the significance of the results for patients not receiving chemotherapy?

The results demonstrate a substantial survival advantage for patients not receiving chemotherapy, indicating Multikine could meet an unmet medical need for approximately 155,000 patients diagnosed annually.

What is the next step for CEL-SCI after the trial results?

CEL-SCI plans to seek FDA approval for Multikine based on the positive outcomes observed in the lower risk subgroup of patients.

What were the safety results reported in the Multikine study?

No safety issues were reported during the trial, indicating a favorable safety profile for Multikine.