CEL-SCI Corporation (NYSE:CVM) has made progress advancing the prerequisites for the upcoming registrational trial, selecting the contract research organization (CRO) that will run it and coming to an agreement with the FDA on which biomarkers are appropriate for selecting patients. The view of oncologists as expressed by the FDA’s ODAC is that using checkpoint inhibitors to treat low PD-L1 expressing patients provides limited efficacy and could even be harmful. This view opens the door for the use of Multikine, if approved, in the low expressing PD-L1 patient population based on its efficacy in this group.
CEL-SCI Milestones
Giovanni Selvaggi joins CEL-SCI as clinical advisor – June 2024
Presentation at the International Drug Discovery Science & Technology (IDDST) Congress – June 2024
CEL-SCI appoints Robert Watson as Chairperson of the Board – July 2024
Feedback from various regulatory agencies - 2024
Submission of license application to various agencies – 2024+
Grant of pediatric waiver by UK’s MHRA – September 2024
UK’s MHRA grants pediatric waiver to Multikine – September 2024
Ergomed selected as CRO for confirmatory trial – October 2024
FDA ODAC opines against use of checkpoints in low PD-L1 expression patients – October 2024
FDA agrees to use of PD-L1 biomarker in Multikine registration study – November 2024
ESMO Poster Presentation
On September 16th, 2024, Dr. József Tímár, presented a poster entitled “Prognostic significance of diagnostic staging in treatment naïve, resectable locally advanced primary oral cavity squamous cell carcinoma for neoadjuvant Leukocyte Interleukin Injection immunotherapy.” He presented at the European Society for Medical Oncology (ESMO) 2024 Congress which was held in Barcelona, Spain. The poster presented graphical data comparing high risk and low risk subjects who were evaluated in the IT-MATTERS trial measuring the probability of overall survival (OS) over time. The subpopulation included in the data set consisted of 114 subjects who met the target population selection criteria. The high-risk group included patients that presented a high risk of cancer recurrence and who were recommended to undergo chemotherapy following surgery (N=35). The low risk group included patients that were recommended to be given radiotherapy but not chemotherapy after surgery (N=79). Both groups showed a survival benefit for the Multikine arm.
The 79 patients who were recommended to receive only radiotherapy benefited to an even greater degree from pre-surgery treatment with Multikine compared to the wider 114 patient group. This target low risk population (n=38) had a 5-year overall survival of 82.6% when treated with Multikine vs. 47.3% when treated with standard of care alone (n=41), without overlap in their respective 95% confidence intervals. More recent analysis for the target low risk population (n=79) produced a hazard ratio of 0.27 (95% CI [0.12, 0.64], Wald p=0.0027) achieving a 73% reduction in overall risk of death.
While the overall survival benefit was clear and statistically significant (log rank p=0.0015) for the entire target population (n=114), the 79 patients who were recommended to receive only radiotherapy benefited to an even greater degree from pre-surgery treatment with Multikine than the group of 114 as a whole. This target low risk population (n=38) had a 5-year overall survival of 82.6% when treated with Multikine vs. 47.3% when treated with standard of care alone (n=41), without overlap in their respective 95% confidence intervals. More recent analysis for the target low risk population (n=79) showed a hazard ratio of 0.27 (95% CI [0.12, 0.64], Wald p=0.0027) achieving a 73% reduction in overall risk of death.
Looking ahead, CEL-SCI management postulated that the use of advanced imaging techniques such as positron emission tomography (PET) may help further improve patient selection and generate a higher success rate for Multikine. PET scans will be used in the upcoming confirmatory registration study for FDA approval.
Clinical Research Organization (CRO) Selection
CEL-SCI selects Ergomed to serve as its CRO for the upcoming confirmatory registration study of Multikine. Details of the selection were included in an October 1st press release. Ergomed had previously provided CRO services to CEL-SCI for the management of the IT-MATTERS trial. Ergomed will manage the trial globally at multiple sites. The announcement reminded readers that the trial will be a 212-patient study enrolling newly-diagnosed, locally advanced, primary head and neck cancer. It will focus on patients with no lymph node involvement and low PD-L1 tumor expression. The anticipated start of the confirmatory trial is 1Q:25.
The FDA’s Oncologic Drugs Advisory Committee (ODAC) convened in September to evaluate the use of checkpoint inhibitors in different cancers and when certain therapies are appropriate depending on biomarker readings. The ODAC is a panel of expert advisors that provides recommendations to the FDA regarding cancer drugs and treat-ments. The committee consists of medical experts, oncologists, researchers, and other healthcare professionals specializing in cancer treatment whose primary role is to review and evaluate new cancer drugs, therapies, and treatments before they are approved for market use.
The ODAC provided an opinion on adequacy of PD-L1 expression as a predictive biomarker for patient selection in this patient population, risk-benefit assessments in different subpopulations defined by PD-L1 expression and ade-quacy of the cumulative data to restrict the approvals of immune checkpoint inhibitors based on PD-L1 expression. After reviewing the data, the ODAC voted 10-2 and 11-1 against the risk-benefit profile for PD-L1 inhibitors in various cancers in two separate votes. Committee members expressed concerns about the lack of benefit demonstrated for patients with low PD-L1 expression, while some members pointed to evidence that the use of the imm-une checkpoint inhibitors may add unnecessary toxicities for patients while also increasing financial burdens on patients. If our readers suffer from insomnia, a solution can be found in the near nine hour meeting on YouTube.
The ODAC’s view opens the door for products such as Multikine that work better in low expression PD-L1 tumors and could be a complement or alternative to checkpoint inhibitors for treatment of non-responsive patients.
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