Confirmatory Phase 3 Trial Designed to Support Commercialization of Multikine for Head and Neck Cancer Treatment
Full enrollment expected by Q2 2026 with plans to seek early approval at that time based on early tumor responses—Potential to set a new standard of care

CEL-SCI Corporation (NYSE:CVM) today announced it is in the final stages for the launch of its 212-patient Confirmatory Registration Study for Multikine* (Leukocyte Interleukin, Injection) in newly diagnosed locally advanced head and neck cancer patients. This final Registration Study is specifically designed to confirm the statistically significant efficacy and safety results from CEL-SCI's previously completed randomized controlled Phase 3 trial.

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Multikine is given via injection for 3 weeks after diagnosis and before surgery. The pre-surgical tumor responses shown in the chart demonstrate that patients whose tumors shrink in response to Multikine are more likely to have longer survival. (Graphic: Business Wire)

This new Registration Study targets the population of previously untreated resectable stage 3 and 4 head and neck cancer patients who had no lymph node involvement and low PD-L1 tumor expression. During the completed Phase 3 clinical trial, the 5-year survival rate of the target patient population increased to 73% when patients were treated with Multikine vs 45% for control patients who received only the standard of care treatments.

Key aspects of the new Confirmatory Registration Study are as follows:

Enlisting clinical sites and investigators in numerous countries across 3 continents
Full enrollment expected by Q2 2026 with plans to seek early approval at that time based on early tumor responses—Potential to set a new standard of care
FDA concurred with the overall design of the Registration Study in meetings last year
Final clinical protocol submitted to FDA in December 2024
Multikine extended median overall survival by nearly 4 years in prior Phase 3 study
A new model for healthcare—Immunotherapy given before surgery to boost the immune system and make the first cancer treatment more successful - may set the first new standard of care in more than half a century

"Now that the clinical protocol for our final marketing Registration Study has been submitted, we are proceeding to sign up investigators and open clinical sites. We are receiving a very positive response and high levels of interest from head and neck cancer physicians who see the abundance of data on Multikine and want to deliver this option to their patients," stated CEL-SCI CEO Geert Kersten. "We believe that this small 212-patient trial will enroll relatively quickly precisely because Multikine has proven what it can do in terms of safety and efficacy in this specific target patient population which has not had a new option for treatment in decades."

"We are very confident in this Registration Study's chance of success since we already know that this type of patient showed an almost 4 year increase in median survival in our last study. The many studies we have done have helped us figure out who benefits from the drug and who does not. Early tumor responses measured after treatment with Multikine and prior to surgery have been shown to be correlated with 5-year overall survival outcomes. We plan to seek accelerated and/or conditional marketing approval based on this finding. Data regarding early tumor responses following Multikine treatment should become available shortly after the last patient has been treated, expected by the second quarter of 2026," Kersten concluded.

CEL-SCI has been advised by a biostatistician with expertise in the design and analysis of oncology studies that this final Confirmatory Registration Study has an over 95% chance of success because it will include only the target population of patients who benefited most from Multikine in the prior Phase 3 study. These patients had much longer overall survival and had tumor responses including size reduction and total tumor elimination confirmed by pathology following three weeks of Multikine treatment. The favorable efficacy results in this target patient population exhibited a hazard ratio of 0.35 with an upper 95% confidence interval of 0.66, therefore CEL-SCI can expect (at 95%) to reach a favorable hazard ratio in the Confirmatory Registration Study.

There were no safety signals identified, Multikine administration did not interfere with disease directed treatment/therapy, and Multikine did not add to the treatment burden imparted by the standard of care.

Following the U.S. Food and Drug Administration's (FDA) go-ahead to conduct the Registration Study, CEL-SCI finalized the clinical protocol based on constructive comments from FDA reviewers and senior staff. The final clinical protocol was submitted to the FDA in December 2024. The study is titled:

"A Phase III, Open Label, Randomized, Controlled, Multi-Center Study of the Effects of Neoadjuvant Leukocyte Interleukin, Injection (LI) Plus Standard of Care Versus Standard of Care Only in Treatment Naïve Adults With Resectable Locally Advanced Primary Squamous Cell Carcinoma of the Head and Neck (Oral Cavity) Who Present With No Nodal Involvement and Low Tumor Programmed Death Ligand 1 Expression (Defined as Tumor Proportion Score <10)"

Ergomed, the clinical research organization (CRO) for the Registration Study, is currently identifying clinical sites and investigators. Sites are initially expected to open in four countries across three continents, with the first clinical site expected to initiate in the United States.

About CEL-SCI Corporation

CEL-SCI believes that boosting a patient's immune system before surgery, radiotherapy and chemotherapy have damaged it should provide the greatest possible impact on survival. Multikine is designed to help the immune system "target" 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.

Multikine (Leukocyte Interleukin, Injection), given right after diagnosis and before surgery, has been dosed in over 740 patients and received Orphan Drug designation from the FDA for neoadjuvant therapy in patients with squamous cell carcinoma (cancer) of the head and neck. Based on the data from the completed randomized controlled Phase 3 study, the FDA concurred with CEL-SCI's target patient selection criteria and gave the go-ahead to conduct a confirmatory Registration Study. The study will enroll 212 newly diagnosed locally advanced primary treatment naïve resectable head and neck cancer patients with no lymph node involvement (determined via PET scan) and with low PD-L1 tumor expression (determined via biopsy), representing about 100,000 patients annually.

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. 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, 2024. 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. 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/20250220081468/en/

Gavin de Windt

(703) 506-9460

CEL-SCI Corporation

CEL-SCI to Initiate Multikine Confirmatory Phase 3 Cancer Trial