The immunotherapy Leukocyte interleukin followed by surgery and radiotherapy, without chemotherapy, significantly improved overall survival compared with standard of care alone in the treatment of patients with advanced primary squamous cell carcinoma of the head and neck.
The immunotherapy Leukocyte interleukin (Multikine) followed by surgery and radiotherapy, without chemotherapy, significantly improved overall survival (OS) compared with standard of care (SOC) alone in the treatment of patients with advanced primary squamous cell carcinoma of the head and neck (SCCHN), according to data from a landmark phase 3 trial.1
In the intent-to-treat (ITT) population of patients with advanced primary SCCHN, the Multikine treatment regimen yielded an OS benefit of 14.1% (HR, 0.68; P = .0236); the OS rate at 5 years was 62.7% in patients who received the regimen followed by surgery and radiotherapy, but not chemotherapy, as part of SOC. Notably, the OS benefit derived with this approach was found to increase over time, with a robust and durable duration effect found to exceed 5 years.
Patients who received the same Multikine regimen before surgery and radiotherapy, but also received chemotherapy, did not experience the same survival advantage. The chemotherapy, which was cisplatin, was administered intravenously and is hypothesized to have negated the benefit imparted with the Multikine product in this population.
Specifically, the 3-year OS rate with Multikine plus cyclophosphamide, indomethacin, and zinc-multivitamins (CIZ) and SOC was 72.4% vs 78.8% with Multikine (no CIZ) and SOC, and 67.5% with SOC alone. The 5-year OS rates in these groups were 62.7% vs 55.5% vs 48.6%, respectively. The primary survival comparison was predefined to examine only the first and last groups.
When the overall study population to which the Multikine regimen was given (combined lower risk [no chemotherapy] and higher risk [with chemotherapy]) and was compared with the control, the study was not found to achieve its primary end point of an OS improvement of 10%. However, the benefit of 14.1% at 5 years in the lower-risk subset who did not receive chemotherapy exceeded the 10% OS benefit that was set for the overall study population and was determined to have clinical significance.
As such, CEL-SCI Corporation has announced plans to seek FDA approval for the use of this regimen in this patient population who did not receive chemotherapy as part of their SOC.
“Multikine demonstrated a significant survival benefit in the group whose SOC did not include chemotherapy and a favorable safety profile across the entire patient population. Based on these 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,” Geert Kersten, chief executive officer of CEL-SCI Corporation, stated in a press release. “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 OS.”
A total of 928 patients with stage III and IVa disease were enrolled to the global phase 3 study, which was conducted at 78 clinical sites throughout 3 continents. Of the 928 patients, 923 comprised the ITT population because 5 patients never received treatment.
Patients received either a Multikine treatment regimen with CIZ and SOC vs SOC alone. In each comparator arm, participants were determined by pathology following surgery to receive radiotherapy only or concurrent chemotherapy. Treatments were prescribed by the protocol and were based on guidelines issued by the National Comprehensive Cancer Network for the treatment of patients with SCCHN. Data were examined per the trial protocol and the Statistical Analysis Plan.
“These data, combined with what we know of Multikine’s mechanism of action, demonstrate Multikine’s potential to impart long-term OS advantage and a beneficial effect on the antitumor immune response in patients who have not been treated with chemotherapy (cisplatin), which is known to be highly toxic,” Eyal Talor, PhD, chief scientific officer of CEL-SCI Corporation, added in the release. “In patients not indicated to receive chemotherapy as part of their SOC, treatment with Multikine neoadjuvant regimen demonstrated a statistically significant, robust, and durable OS benefit. The data possibly indicate that the Multikine treatment regimen is capable of altering the course of disease in this population.”