CEL-SCI Corporation has achieved a significant milestone in advancing its immunotherapy candidate Multikine, receiving FDA clearance for a pivotal confirmatory registration study in head and neck cancer patients. The carefully designed trial will focus on newly diagnosed patients with squamous cell carcinoma of the head and neck (SCCHN) who have no lymph node involvement and low PD-L1 tumor expression.
Trial Design and Patient Selection
The upcoming study will enroll 212 patients in a two-arm, two-stage, 1:1 randomized controlled trial. The trial's primary endpoint will measure overall survival (OS), with an initial stage examining pre-surgical response rates. To achieve regulatory approval, the study must demonstrate at least a 10% improvement in overall survival with a hazard ratio of 0.72 or less.
The patient selection criteria were developed based on promising data from the previous IT-MATTERS study, which showed remarkable results in a similar population. In that trial, Multikine-treated patients achieved a 73% survival rate compared to 45% in the control group at the five-year mark, with a statistically significant p-value of 0.0015 and a hazard ratio of 0.35.
Regulatory Progress and Global Strategy
The company has made substantial progress on the regulatory front, with both the European Medicines Agency (EMA) Pediatric Committee and the United Kingdom's Healthcare Products Regulatory Agency (MHRA) granting Multikine a pediatric waiver. This development streamlines the potential approval process in these key jurisdictions.
Dr. Giovanni Selvaggi, who joined CEL-SCI as clinical advisor in June 2024, commented on the trial design: "The careful selection of patients based on lymph node status and PD-L1 expression represents a precision medicine approach that could maximize the benefit for head and neck cancer patients."
Operational and Financial Preparations
CEL-SCI has selected Ergomed, which previously managed the IT-MATTERS trial, as the Contract Research Organization (CRO) to oversee the global study. The trial is scheduled to begin in the first quarter of 2025, with full enrollment expected by the second quarter of 2026.
The company recently secured $5 million through a stock offering, selling 16,130,000 shares at $0.31 per share. The total estimated cost for the confirmatory trial is $30 million. For the fiscal year 2024, CEL-SCI reported research and development expenses of $18.2 million, reflecting a 19% decrease from the previous year.
Scientific Rationale and Clinical Significance
The biological rationale for Multikine's use centers on its administration before surgery when patients' immune systems remain strong. The therapy has demonstrated significant tumor regression rates in both Phase II and Phase III studies, with no excess toxicity beyond the standard of care.
Robert Watson, recently appointed as Chairperson of the Board, stated, "The confirmatory trial design, backed by strong preliminary data and clear regulatory guidance, positions Multikine to potentially address a significant unmet need in head and neck cancer treatment."
