Autologous TIL Cell Therapy: A Potential Next Line of Treatment for HNSCC

Results from the phase 2 study C-145-03 (NCT03083873) suggest the role of autologous tumor-infiltrating lymphocyte (TIL) therapy in treating and stabilizing recurrent and or metastatic head and neck squamous cell carcinoma (HNSCC), revealing potential to serve as a next line of treatment after immunotherapy and chemotherapy.^1,2

The study modestly met its primary end point with an objective response rate (ORR) of 11% (95% CI, 4.3%–23.0%), demonstrating the role of the therapy in promoting antitumor activity. The median duration of response (DOR) was 7.6 months over a median follow-up of 17.9 months. Furthermore, evidence also shows the therapy’s potential for disease control and stabilization, with a disease control rate (DCR) of 76% (95% CI, 61.7%–86.2%) and 64% of patients (n = 34) having stable disease.

“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 Robert L. Ferris, executive director of University of North Carolina Lineberger Comprehensive Cancer Center and first author, in a press release.¹

Regarding safety, almost all patients (98%) experienced treatment-emergent adverse events (TEAEs). The most frequent AEs reported were chills (60%), hypotension (53%), fever (47%), hypophosphatemia (42%), febrile neutropenia (42%), and hypocalcemia (33%).

What Was the C-145-03 Study Evaluating?

C-145-03 was a phase 2, multicenter, nonrandomized, prospective, open-label trial that took place across 22 sites in the United States over 5 years, between January 2017 and August 2022.³ It evaluated the performance of autologous TIL cell therapy in 53 adult patients with recurrent and or metastatic HNSCC who had received 1 to 3 lines of prior immunotherapy and or chemotherapy. Patients were assigned to 1 of 4 treatment cohorts, receiving a one-time infusion of a TIL variant: noncryopreserved TIL (n = 8), cryopreserved lifileucel (Amtagvi) with 22-day manufacturing (n = 17), cryopreserved lifileucel with 16-day manufacturing (n = 16), and cryopreserved LN-145-S1 PD-1 (n = 12). Prior to treatment, patients underwent tumor resection and nonmyeloablative lymphodepletion. Following TIL infusion, a short course of high-dose interleukin-2 (IL-2) was administered.

What Are the Unmet Needs in HNSCC?

The study aimed to address the high rate of recurrence of HNSCC after first-line treatment.² Prior research has found that disease recurrence tends to occur in HNSCC patients with low or moderate TIL levels compared with those who have high TIL levels.^1,2

According to the investigators, there are currently “few effective treatment options in patients who experience disease progression on or after [immune checkpoint inhibitor] therapy.”² The study data suggest that autologous TIL cell therapy may help feasibly fill this gap by slowing disease progression, especially among patients whose condition did not respond sufficiently to prior treatment, and ultimately prolonging survival.

What Are the Next Steps in Research?

Study limitations noted by the investigators were the nonrandomized design and small sample sizes for comparison across treatment cohorts. Overall, while the investigators determined that the outcomes do not support further clinical development, they urged the need for a randomized trial to measure the performance of autologous TIL cell therapy against the current standards of care, and for future development of combination therapies that can optimize the efficacy of the therapy.²

“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,” concluded Ferris in the press release.¹

REFERENCES:

1. Immune cell therapy for advanced head and neck cancer helps stabilize disease. News release. University of North Carolina Lineberger Comprehensive Cancer Center. Published August 26, 2025. Accessed September 11, 2025. https://tinyurl.com/35d9wuak

2. Ferris RL, Leidner RS, Chung CH, et al. Efficacy and safety of one-time autologous tumor-infiltrating lymphocyte cell therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. J Immunotherap Canc. 2025;13(8):e011633. doi: 10.1136/jitc-2025-011633

3. Study of LN-145/​LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck. ClinicalTrials.gov. Updated October 12, 2023. Accessed September 11, 2025. https://clinicaltrials.gov/study/NCT03083873