A long-term data readout from the phase 3 IT-MATTERS trial highlighted the potential of leukocyte interleukin injection as a treatment for patients with locally advanced primary squamous cell carcinoma of the head and neck, oral cavity, and soft palate.
Long-term follow-up data highlighted the promise of leukocyte interleukin injection (Multikine) peritumorally plus perilymphatically and a non-chemotherapeutic dose of cyclophosphamide (CIZ) followed by standard of care in a population of patients with previously untreated locally advanced primary squamous cell carcinoma of the head and neck (SCCHN), oral cavity, and soft palate, according to findings from the phase 3 IT-MATTERS trial (NCT01265849) published on ClinicalTrials.1,2
Investigators reported that within the intent-to-treat (ITT) population, the overall response rate (ORR) in the experimental arm was 8.1% (n = 32/395) compared with 0.0% in the standard of care (SOC) population (n = 0/394). Additionally, in the population of patients at a lower risk of recurrence, the ORR was 15.2% (n = 24/158) in the injection and CIZ arm compared with 0.0% in the standard of care arm (n = 0/168; 2-sided Fisher Exact P-value <.0000001). A total of 5 patients in the experimental arm experienced complete responses.
A total of 928 patients were included in the study to assess the efficacy and clinical benefit of leukocyte interleukin injection in a population of patients with locally advanced primary squamous cell carcinoma of the head and neck, oral cavity, and soft palate. The injection utilizes naturally occurring, immune-regulating cytokines, and could be the first investigational immunotherapeutic to be used in the first-line neoadjuvant setting in a previously untreated population prior to standard of care.
A total of 3 randomized treatment arms were included in the study: 3 consecutive weeks of supraphysiologic doses of the injection 5 times per week both peritumorally and perilymphatically plus CIZ following by standard of care and zinc multivitamins daily from day 1 of injection to 1 day prior to surgery (n = 3/7); 3-week injection regimen minus CIZ prior to standard of care (n = 1/7); and standard of care alone (n = 3/7). Standard of care was identical across all arms and consisted of a bifurcated treatment path after surgery, including a radiotherapy-only cohort and concurrent chemoradiotherapy cohort. Treatment strategy was determined based on pathology and medical judgment.
Additional findings from the study that will be presented to the FDA indicated that objective response prior to surgery appeared predictive of improved overall survival (OS) and a significant reduction in mortality. For the ITT population, the death rate was 22.2% among leukocyte interleukin injection responders compared with 54.1% in non-responders (HR, 0.301; 95% CI, 0.16-0.566; 2-sided Fisher Exact P-value <.0001). In patients who had lower risk of recurrence, these rates were 12.5% vs 41.0% in both respective arms (HR, 0.246; 95% CI, .077-.787; 2-sided Fisher Extract P-value = .0101).
Investigators also reported a 5-year OS benefit of 14.1% in the experimental arm among those at a lower risk of recurrence, with OS rates of 62.7% compared with 48.6% in the standard of care arm. Additionally, the median OS in the lower risk of recurrence population was 101.7 months in the peritumoral injection plus CIZ arm compared with 55.2 months in the standard of care arm. Investigators also reported confirmation of progression-free survival for patients within the lower risk of recurrence cohort among those treated with the injection plus CIZ compared with standard of care. Moreover, the incidence of adverse effects (AEs) and serious AEs were comparable between the 2 treatment arms.