CEL-SCI Corporation has announced FDA approval to proceed with a confirmatory registration study of Multikine for head and neck cancer. The trial will enroll 212 patients with newly diagnosed, locally advanced primary (stage III and IVa) head and neck cancer who have no lymph node involvement and low PD-L1 tumor expression. This decision follows promising results from a previous Phase 3 study where Multikine demonstrated a 73% survival rate compared to 45% in control groups.
The confirmatory study aims to validate Multikine's efficacy in a specific patient population identified through retrospective analysis of the Phase 3 trial data. These patients, characterized by the absence of lymph node involvement (N0) and low PD-L1 tumor expression, showed a statistically significant survival benefit (p=0.0015) with a hazard ratio of 0.35 in the prior study.
Biological Rationale
CEL-SCI emphasizes the biological rationale behind the selection criteria for the confirmatory study. Multikine, an immunotherapy, is designed to stimulate the patient’s immune system to target the tumor. The company hypothesizes that administering Multikine before surgery, radiotherapy, or chemotherapy—when the immune system is still intact—will yield the best results.
Geert Kersten, CEO of CEL-SCI Corporation, stated, “Our goal is to make the first cancer treatment more successful by activating an anti-tumor immune response BEFORE surgery, radiotherapy and chemotherapy weaken the immune system.”
Prior Phase 3 Trial Results
While the Phase 3 study missed its primary endpoint of a 10% improvement in overall survival in the intent-to-treat population, a subgroup analysis revealed a significant survival benefit in patients who received Multikine followed by surgery and radiotherapy. Specifically, this group experienced a 46.5-month overall survival benefit compared to the control group (101.7 months vs. 55.2 months).
Notably, patients who received chemotherapy in addition to radiotherapy after surgery did not show a survival benefit. This observation led CEL-SCI to develop selection criteria to identify patients most likely to benefit from Multikine as a neoadjuvant (pre-surgery) treatment.
Study Design and Patient Selection
The confirmatory study will focus on patients with newly diagnosed locally advanced primary head and neck cancer (stage III and IVa) who meet the following criteria:
- No lymph node involvement (N0), determined via PET imaging.
- Low PD-L1 tumor expression, determined via biopsy.
CEL-SCI believes that these criteria will identify patients in whom Multikine's mechanism of action—stimulating an anti-tumor immune response—will be most effective. The company also notes that in the Phase 3 study, Multikine treatment led to significant rates of tumor regression, including five complete regressions, before surgery, following just three weeks of treatment.
Addressing Criticisms of Subgroup Analysis
CEL-SCI has proactively addressed potential criticisms related to subgroup analyses. The company emphasizes that the selection criteria were pre-specified in the statistical analysis plan (SAP) and are supported by a strong biological rationale. The statistical significance (p=0.0015) observed in the subgroup analysis further strengthens the validity of the findings.
CEL-SCI argues that the selected subgroup's results are directly tied to Multikine’s mechanism of action, providing a strong biological rationale for why this particular group is expected to respond well to pre-surgery treatment. The company also emphasizes that the treatment and control groups in the confirmatory registration study are well-balanced.
Potential Impact
If the confirmatory study is successful, Multikine could become a valuable first-line treatment option for a specific subset of head and neck cancer patients. The focus on pre-surgical treatment aligns with the growing interest in neoadjuvant therapies that aim to improve patient outcomes by targeting the tumor before it can spread or develop resistance to treatment.
