Journal Article

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

Chou, Jeffrey, Ferris, Robert L, Wong, Stuart J, Finckenstein, Friedrich Graf, Lee, Sylvia M, Grilley-Olson, Juneko E, Redman, Rebecca, Jimeno, Antonio, Cohen, Ezra E W, Sukari, Ammar, Nieva, Jorge J, Misleh, Jamal, Villaflor, Victoria M, Catlett, Melissa, Chung, Christine H, Gastman, Brian, Leidner, Rom S, Fiaz, Rana, Yi, Min

2025

Overview

BackgroundRecurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a high recurrence rate after first-line immunotherapy or chemoimmunotherapy. The presence of a high density of tumor-infiltrating lymphocytes (TILs) in HNSCC tumors was shown to be associated with improved clinical outcomes. One-time autologous TIL cell therapy was evaluated in patients with recurrent and/or metastatic HNSCC.MethodsC-145-03 (NCT03083873) was a phase 2 study of TIL in patients with recurrent and/or metastatic HNSCC assigned to 1 of 4 treatment cohorts: cohort 1, non-cryopreserved TIL; cohort 2, cryopreserved lifileucel (22-day manufacturing); cohort 3, cryopreserved lifileucel (16-day manufacturing); cohort 4, cryopreserved LN-145-S1 programmed cell death protein-1 (PD-1) selected. Patients underwent tumor resection for TIL generation. After preparative non-myeloablative lymphodepletion, patients received a single infusion of TIL followed by interleukin-2 (IL-2) infusion(s). The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria for Solid Tumors (RECIST) V.1.1. Secondary endpoints were investigator-assessed duration of response (DOR), disease control rate (DCR), progression-free survival, overall survival, and incidence of treatment-emergent adverse events.ResultsOverall, 53 patients received TIL: cohort 1 (n=8), cohort 2 (n=17), cohort 3 (n=16), cohort 4 (n=12). Median age was 57 years and most patients were males (87%; 46/53) with stage IV disease (98%; 52/53). Patients had a median of two prior lines of systemic therapy; 87% (46/53) of patients had prior anti-PD-1/programmed cell death ligand-1 therapy and 72% (38/53) had prior chemotherapy. The ORR was 11% (6/53) with six patients achieving partial response (cohort 1, n=3; cohort 2, n=1; cohort 4, n=2). At median follow-up of 17.9 months, the median DOR was 7.6 months. The DCR was 76% (40/53); 64% (34/53) of patients had stable disease. The safety profile was consistent with known toxicities associated with non-myeloablative lymphodepletion and IL-2 administration.ConclusionsThis study demonstrated the feasibility of consistently generating sufficient TIL from HNSCC tumors. Results from this study suggest TIL cell therapy may serve as a potential treatment option for patients with HNSCC and support further development, including TIL cell therapy combined with immune checkpoint inhibitors or other agents or with other TIL products.Trial registration numberNCT03083873.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Aged / Cancer / Cell death / Chemotherapy / FDA approval / Female / Head and Neck Cancer / Head and Neck Neoplasms - immunology / Head and Neck Neoplasms - pathology / Head and Neck Neoplasms - therapy / Humans / Immune Cell Therapies and Immune Cell Engineering / Immune checkpoint inhibitors / Immunotherapy / Lymphatic system / Lymphocytes / Lymphocytes, Tumor-Infiltrating - immunology / Lymphocytes, Tumor-Infiltrating - transplantation / Male / Manufacturing / Melanoma / Metastasis / Middle Aged / Neoplasm Metastasis / Neoplasm Recurrence, Local - immunology / Neoplasm Recurrence, Local - therapy / Original Research / Patients / Response rates / Squamous cell carcinoma / Squamous Cell Carcinoma of Head and Neck - immunology / Squamous Cell Carcinoma of Head and Neck - pathology / Squamous Cell Carcinoma of Head and Neck - therapy / Steroids / Treatment Outcome / Tumor infiltrating lymphocyte - TIL / Tumors