A single administration of autologous tumor-infiltrating lymphocyte (TIL) cell therapy with lifileucel led to disease stability in patients with recurrent and/or metastatic head and neck squamous cell carcinoma, even among patients whose disease had progressed or did not respond to multiple prior treatments, according to findings from a phase II trial published in the Journal for the ImmunoTherapy of Cancer.
The results of the study support further development of lifileucel for patients with head and neck squamous cell carcinoma, including as part of a combination regimen.
“This study demonstrated the feasibility of consistently generating TILs from recurrent and or metastatic head and neck squamous cell carcinoma tumors to stabilize a patient’s disease,” said corresponding author Robert L. Ferris, MD, PhD, Executive Director of the UNC Lineberger Comprehensive Cancer Center.
Study Methods and Rationale
Autologous TIL cell therapy was explored in patients with recurrent and/or metastatic head and neck squamous cell carcinoma as a high density of TILs was previously shown to be associated with improved clinical outcomes.
The C-145-03 trial was a phase II study of TIL cell therapy with lifileucel in four treatment cohorts in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (n = 53). Cohort 1 included treatment with noncryopreserved tumor-infiltrating lymphocytes, cohort 2 received cryopreserved lifileucel with 22-day manufacturing, cohort 3 received cryopreserved lifileucel with 16-day manufacturing, and cohort 4 received PD-1–selected cryopreserved TILs (LN-145-S1).
All patients underwent tumor resection for generation of TILs. Patients received a preparatory nonmyeloablative lymphodepleting regimen followed by a single infusion of TILs and then interleukin-2 infusion.
Key Study Findings
The overall objective response rate was 11%, including partial responses in six patients, including three from cohort 1, one from cohort 2, and two from cohort 4. The disease control rate was 76%. Sixty-four percent of patients had stable disease.
Patients were followed for a median of 17.9 months and the median duration of response was 7.6 months. The median overall survival was 9.5 months.
The safety profile was consistent with already known adverse events from nonmyeloablative lymphodepletion and interleukin-2 administration. The most common non–blood-related adverse events were chills in 60% of patients, low blood pressure in 53%, and fever in 47%. Common blood-related adverse events included low platelet counts in 74% of patients and anemia in 53%.
“This trial has been a crucial step in not only finding a way to stabilize a patient’s disease but also to help guide us to the next stage of discovery, which is how to further prolong these patients’ lives while providing them with the best possible quality of life,” Dr. Ferris concluded.
Ferris RL, et al: J Immunother Cancer 13:e011633, 2025.
