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Clinical Trial
. 2025 Aug 24;13(8):e011633.
doi: 10.1136/jitc-2025-011633.

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

Robert L Ferris MD,  1 , Rom S Leidner  2 , Christine H Chung  3 , Antonio Jimeno  4 , Sylvia M Lee  5 , Ammar Sukari  6 , Jorge J Nieva  7 , Juneko E Grilley-Olson  8 , Rebecca Redman  9 , Stuart J Wong  10 , Victoria M Villaflor  11 , Jamal Misleh  12 , Friedrich Graf Finckenstein  13 , Jeffrey Chou  13 , Brian Gastman  13 , Rana Fiaz  13 , Melissa Catlett  13 , Min Yi  13 , Ezra E W Cohen  14
Affiliations
Clinical Trial

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

Robert L Ferris MD, et al. J Immunother Cancer. .

Abstract

Background: Recurrent 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.

Methods: C-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.

Results: Overall, 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.

Conclusions: This 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 number: NCT03083873.

Keywords: Head and Neck Cancer; Immunotherapy; Tumor infiltrating lymphocyte - TIL.

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Conflict of interest statement

Competing interests: RLF: Consulting, Advisory: Addgene, Adaptimmune, Aduro Biotech, Bicara Therapeutics, Bristol Myers Squibb, Brooklyn Immunotherapeutics LLC, Catenion, Coherus BioSciences, CureVac, CytoAgents, Eisai Europe, EMD Serono, Everest Clinical Research, F Hoffmann-La Roche, Federation Bio, Genocea Biosciences, Genmab, Hookipa Biotech GmbH, Instil Bio, Kowa Research Institute, Lifescience Dynamics, MacroGenics, MeiraGTx LLC, Merck, Merus NV, Mirati Therapeutics, Nanobiotix, Novartis Pharmaceutical, Novasenta, Numab Therapeutics AG, OncoCyte Corporation, Pfizer, PPD Development LP, Rakuten Medical, Regeneron, Sanofi, Seagen, SIRPant Immunotherapeutics, Vir Biotechnology, Zymeworks; Clinical Trial, Research Funding: AstraZeneca/MedImmune, Bristol Myers Squibb, Merck, Novasenta, Tesaro; Data Safety Monitoring Board: Mirror Biologics. RSL: Consulting, Advisory: Bristol Myers Squibb, Merck, CDR-Life, Vir, AstraZeneca, RAPT, Incyte; Research Funding: Bristol Myers Squibb, Incyte, AstraZeneca; Travel, Accommodations, Expenses: Bristol Myers Squibb. CHC: Advisory Board: AVEO, Bicara Therapeutics, Exelisis, Fulgent, Seagen; Paid Consultant: Genmab, Regeneron; Research Grant (institution): Acrivon, Regeneron. AJ: Consulting: Bluedot Bio, Purple Biotech, Transimmune; Grants: NCI R01CA149456, R01DE024371, and P50CA261605; Institutional Contracts: Cantargia, Debiopharm, Genentech, Iovance, Khar Biopharma, Merck, Moderna, Pfizer, Sanofi, and SQZ for trials where he is the local PI. SML: Institutional support for clinical trials: Iovance, Lyell, Pfizer, Black Diamond. AS: Consulting: EMD Serono; Speaker: Merck. JJN: Consulting: Aadi Biosciences, ANP Technologies, AstraZeneca, BioAtla, G1 Therapeutics, Genentech, KaliVir, MindMed, Naveris, Sanofi; Research Funding: Genentech, Merck; Intellectual Property: Cansera; Stock or Stock Options: AffyImmune, Amgen, Cansera, Epic Sciences, Indee Bio, Johnson & Johnson, Novartis. JEG-O: Consulting: Aadi, Deciphera, Ipsen; Research Funding: Boehringer Ingelheim, Inhibrx, PTC therapeutics. RR: Funding to institution for clinical trial support: Coherus BioSciences, Dragonfly, Merck, Molecular Templates, RAPT Therapeutics. SJW: Invited Speaker: Merck Sharp & Dohme, Bristol Myers Squibb, Sanofi, Sun Pharma, Pierre Fabre, and AstraZeneca; Advisory Board: Bristol Myers Squibb, and Philogen; Research Grant: Novartis; Consulting/Advisory Role: Merck Sharp & Dohme, Bristol Myers Squibb, Sanofi, and Sun Pharma; Travel, Accommodations, Expenses: Pierre Fabre and Sun Pharma. VMV: Advisory: AstraZeneca, Coherus BioSciences, Regeneron; Research Support: Takeda. JM: Nothing to disclose. FGF: Employment: Iovance Biotherapeutics; Stock or Stock Options: Iovance Biotherapeutics; Travel, Accommodations, Expenses: Iovance Biotherapeutics; Patents, Royalties, Other Intellectual Properties: Bristol Myers Squibb. JC: Employment: Iovance Biotherapeutics; Stock or Stock Options: Iovance Biotherapeutics; Travel, Accommodations, Expenses: Iovance Biotherapeutics. BG: Employment: Iovance Biotherapeutics; Stock or Stock Options: Iovance Biotherapeutics; Travel, Accommodations, Expenses: Iovance Biotherapeutics. RF: Employment: Iovance Biotherapeutics; Stock or Stock Options: Iovance Biotherapeutics; Travel, Accommodations, Expenses: Iovance Biotherapeutics. MC: Employment: Iovance Biotherapeutics; Stock or Stock Options: Iovance Biotherapeutics; Travel, Accommodations, Expenses: Iovance Biotherapeutics. MY: Employment: Iovance Biotherapeutics; Stock or Stock Options: Iovance Biotherapeutics; Travel, Accommodations, Expenses: Iovance Biotherapeutics. EEWC: Employment: Tempus AI.

Figures

Figure 1
Figure 1. CONSORT diagram. Of the 64 patients enrolled, 53 patients received TIL and were included in the full analysis set and safety analysis set. The full analysis set was defined as patients who received TIL that met the manufacturing product specifications. The safety analysis set was defined as patients who received TIL. aIndicates PD-1-selected cryopreserved TIL. CONSORT, Consolidated Standards of Reporting Trials; PD-1, programmed cell death protein-1; TIL, tumor-infiltrating lymphocyte.
Figure 2
Figure 2. Best percent change from baseline in target lesion sum of diameters by cohort. (A) Percent change from baseline in target lesion sum of diameters for all patients who received TIL. (B) Percent change from baseline (ie, after tumor resection and before lymphodepletion) over time in target lesion sum of diameters for all patients who received TIL. Across cohorts, a total of 6 patients achieved PR, 32 had SD, and 9 had PD. PD, progressive disease; PR, partial response; SD, stable disease; SOD, sum of diameters; TIL, tumor-infiltrating lymphocyte.
Figure 3
Figure 3. Time to response, duration of response, and time on efficacy assessment after TIL therapy. Across cohorts, a total of six patients achieved a confirmed PR and four patients had a DOR of ≥6 months. DOR, duration of response; PR, partial response; TIL, tumor-infiltrating lymphocyte.
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