Leukocyte Interleukin Confirmatory Study Launches in Head and Neck Cancer

An FDA registration-enabling confirmatory registration study of leukocyte interleukin injection (Multikine) as a neoadjuvant treatment for newly diagnosed, previously untreated, resectable, locally advanced primary head and neck cancer will be initiated, according to a news release from the developer, CEL-SCI Corportation.¹ Patient enrollment is expected to begin at clinical centers across the US, Europe, and Asia, with South America to follow; Orient EuroPharma will oversee and fund enrollment within Taiwan.

The confirmatory study will enroll approximately 212 patients with newly diagnosed, previously untreated, resectable, locally advanced squamous cell carcinoma (SCC) of the head and neck whose tumors exhibit low or zero PD-L1 expression and who present with no clinical lymph node involvement at entry. The trial is powered at approximately 97% to confirm a previously observed HR of 0.34 for overall survival (OS) in this population, based on an analysis of the same target subgroup within the completed phase 3 IT-MATTERS trial (NCT01265849). The FDA accepted this patient selection criteria as the trial's target population in May 2024.²

In that target subgroup (n = 114), patients who received a 3-week course of leukocyte interleukin injection prior to standard of care (SOC) had a 73% 5-year OS rate compared with 45% for patients who received SOC alone. The pre-surgical objective response rate (ORR) was 13% in the leukocyte interleukin injection arm vs 0% in the control arm, and pre-surgical downstaging occurred in 35% of interleukin-treated patients compared with 13% who received SOC. Because these early, pre-surgical responses were shown to correlate with long-term OS, the developers intend to use them as early end points to support a potential accelerated or conditional approval application, while OS follow-up continues in a blinded manner until a prespecified event threshold is met.

The broader IT-MATTERS trial, for which findings were published in Pathology and Oncology Research, randomly assigned 923 evaluable patients 3:1:3 to leukocyte interleukin injection plus a non-chemotherapeutic regimen of cyclophosphamide, indomethacin, and zinc (CIZ) followed by SOC; leukocyte interleukin injection plus SOC without CIZ; or SOC alone.³

Across the full intent-to-treat (ITT) population, the trial did not meet statistical significance for its primary end point of OS (462 deaths; 2-sided unstratified log-rank P = .41). Within the subset of patients later classified as low risk for recurrence at surgery (ITT low-risk; n = 380)—a broader, differently defined population than the confirmatory study's PD-L1–low/node-negative target group—leukocyte interleukin injection plus CIZ and SOC showed an OS advantage over SOC alone (HR, 0.68; 95% CI, 0.48-0.95; P = .024), with 5-year OS rates of 62.7% vs 48.6% and a median OS of 101.7 vs 55.2 months.

An early objective response occurred in 8.5% (n = 45/529) of patients who received leukocyte interleukin in the ITT, in 16.0% (n = 34/212) of ITT low-risk treated patients, and no early objective responses (n = 0/394) in the SOC alone group. In the high-risk subgroup, SOC alone outperformed the leukocyte interleukin injection combination, an outcome that investigators attributed to the 3-week treatment delay to surgery required for dosing, which disproportionately disadvantaged higher-risk, faster-growing disease.

"Our confirmatory registration study marks a definitive milestone toward establishing [leukocyte interleukin] as the new immunotherapy standard of care for newly diagnosed head and neck cancer with low or zero levels of PD-L1," said Geert Kersten, chief executive officer of CEL-SCI, in the release.¹ "Backed by approximately 97% statistical power to confirm this survival advantage, we believe this registration-enabling study provides an exceptional opportunity to validate our earlier phase 3 results and bring this much-needed therapy to patients."

Leukocyte interleukin injection is a mixture of naturally occurring cytokines administered peritumorally before surgery, radiation, or chemotherapy. It is designed to stimulate an anti-tumor immune response while a patient's immune system remains intact. It holds FDA orphan drug designation for the neoadjuvant treatment of SCC of the head and neck.

References

1. CEL-SCI to launch FDA registration-enabling phase 3 confirmatory study to bring Multikine® to market for newly diagnosed head and neck cancer. News release. CEL-SCI Corporation. July 13, 2026. Accessed July 13, 2026. https://tinyurl.com/5n77uwy4
2. CEL-SCI receives FDA go-ahead for its confirmatory study of Multikine in the treatment of head & neck cancer. News release. CEL-SCI Corporation. May 8, 2024. Accessed July 13, 2026. https://tinyurl.com/ms54xztc
3. Talor E, Tímár J, Lavin P, et al. Neoadjuvant leukocyte interleukin injection immunotherapy improves overall survival in low-risk locally advanced head and neck squamous cell carcinoma – the IT-MATTERS study. Pathol Oncol Res. 2025;31:1612084. doi:10.3389/pore.2025.1612084