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 (HNSCC), according to findings from a multi-institutional phase II trial published in the Journal for the ImmunoTherapy of Cancer. The results demonstrate therapeutic potential in a patient population with limited treatment options and poor prognosis.
Trial Design and Patient Population
The C-145-03 trial enrolled 53 patients across four treatment cohorts at UNC Lineberger Comprehensive Cancer Center and 21 other U.S. sites. The study evaluated different formulations of TIL therapy: cohort 1 received 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 tumor-infiltrating lymphocytes (LN-145-S1).
Patients had a median age of 57 years, with 98% presenting stage IV disease. The population was heavily pretreated, having received a median of two prior lines of systemic therapy, including prior anti–PD-1/PD-L1 therapy in 87% of cases. All patients underwent tumor resection for generation of tumor-infiltrating lymphocytes, followed by a preparatory nonmyeloablative lymphodepleting regimen, single infusion of tumor-infiltrating lymphocytes, and interleukin-2 infusion.
Clinical Outcomes and Efficacy
The overall objective response rate reached 11%, with partial responses observed in six patients distributed across cohorts 1 (three patients), cohort 2 (one patient), and cohort 4 (two patients). The disease control rate was 76%, with 64% of patients achieving stable disease.
With a median follow-up of 17.9 months, the median duration of response was 7.6 months, with the longest response lasting nearly two years. Median overall survival reached 9.5 months, representing a significant extension for this patient population with historically short life expectancy.
"This is a group of patients with a short life expectancy, many of whom have already undergone chemotherapy, radiation, surgery, and/or immunotherapy, and there are no other known treatments that would have extended life by about 9 months as our TIL therapy did," said corresponding author Robert L. Ferris, MD, PhD, Executive Director of the UNC Lineberger Comprehensive Cancer Center.
Safety Profile
The safety profile was consistent with known adverse events from nonmyeloablative lymphodepletion and interleukin-2 administration. The most common non-blood-related adverse events included chills in 60% of patients, low blood pressure in 53%, and fever in 47%. Blood-related adverse events were primarily low platelet counts in 74% of patients and anemia in 53%. Treatment side effects were described as mostly manageable.
Clinical Significance and Future Directions
The study capitalized on previous findings that HNSCC patients with high levels of TILs demonstrate better clinical outcomes and lower disease recurrence rates. HNSCC accounts for approximately 3.6% of all cancers in the U.S., with an estimated 59,660 new diagnoses and 12,770 deaths expected in 2025, according to the National Cancer Institute.
"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," Ferris noted. The results support further development of lifileucel for patients with head and neck squamous cell carcinoma, including as part of combination regimens.
Future research priorities include optimizing cell expansion methods, determining the optimal choice between fresh or cryopreserved cells, identifying effective combination therapies, and designing randomized trials comparing TIL therapy against current standard of care. The study was sponsored by Iovance Biotherapeutics, which manufactures and markets lifileucel.
