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776 Long-term efficacy and safety of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: a 4-year analysis of the C-144–01 study
  1. Theresa Medina1,
  2. Jason A Chesney2,
  3. Eric Whitman3,
  4. Harriet Kluger4,
  5. Sajeve Thomas5,
  6. Amod A Sarnaik6,
  7. John M Kirkwood7,
  8. James Larkin8,
  9. Jeffrey Weber9,
  10. Omid Hamid10,
  11. Martin Wermke11,
  12. Friedrich Graf Finckenstein12,
  13. Jeffrey Chou12,
  14. Brian Gastman12,
  15. Giri Sulur12,
  16. Xiao Wu12,
  17. Wen Shi13 and
  18. Evidio Domingo-Musibay14
  1. 1University of Colorado Cancer Center Center— Anschutz Medical Campus, Aurora, CO, USA
  2. 2Brown Cancer Center, University of Louisville, Louisville, KY, USA
  3. 3Atlantic Health System, Morristown, NJ, USA
  4. 4Yale Cancer Center, New Haven, CT, USA
  5. 5Orlando Health Cancer Institute, Orlando, FL, USA
  6. 6H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
  7. 7UPMC Hillman Cancer Center, Pittsburgh, PA, USA
  8. 8The Royal Marsden NHS Foundation Trust, London, Chelsea, UK
  9. 9Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, USA
  10. 10The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Los Angeles, CA, USA
  11. 11Technical University Dresden – NCT/UCC Early Clinical Trial Unit, Dresden, Germany
  12. 12Iovance Biotherapeutics, Inc, San Carlos, CA, USA
  13. 13Iovance Biotherapeutics, San Carlos, CA, USA
  14. 14Masonic Cancer Center, Minneapolis, MN, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Immune checkpoint inhibitors (ICI) have improved outcomes for patients with metastatic melanoma; nevertheless, resistance is common and subsequent treatment options are limited. Lifileucel, a one-time autologous TIL cell therapy, achieved a 31.4% objective response rate (ORR) with a median duration of response (DOR) not reached at a median of 36.5 months of follow-up, in patients with advanced (unresectable or metastatic) melanoma who progressed after ICI and targeted therapy (if appropriate; Sarnaik SITC 2022). We report updated, long-term follow-up data on lifileucel treatment outcomes from C-144–01, representing the largest population of patients with anti-PD-1-refractory advanced melanoma treated with TIL cell therapy.

Methods C-144–01 (NCT02360579) is a prospective, open-label, multicohort, multicenter, nonrandomized phase 2 study; this 4-year update includes investigator-assessed efficacy data from patients in Cohorts 2 and 4 (combined due to identical eligibility, lifileucel manufacturing process, and treatment regimen). Patients had ≥1 lesion(s) resected (~1.5 cm diameter) for 22-day cryopreserved lifileucel manufacturing. The treatment regimen included preparative lymphodepletion (cyclophosphamide 60 mg/kg/d × 2d, fludarabine 25 mg/m2/d × 5d), a single lifileucel infusion, and up to 6 doses of high-dose IL-2 (600,000 IU/kg). Investigators assessed response per RECIST v1.1.

Results As of the data cutoff (16 June 2023), median study follow-up was 48.1 months. Median overall survival (OS) was 13.9 months (95% CI: 10.6 to 17.8). One-, 2-, 3-, and 4-year OS rate was 54.0%, 33.9%, 28.3%, and 22.2%, respectively. Forty-eight of 153 (31.4%) lifileucel-treated patients achieved an investigator-assessed objective response; 54.2%, 39.6%, 33.3%, and 20.8% of responses lasted ≥12, ≥24, ≥36, and ≥48 months, respectively (figure 1). Twelve responses (25.0%) were ongoing at time of analysis and longest response was ongoing at 59.9 months. Treatment-emergent adverse events (AEs) were consistent with known safety profiles of lymphodepletion and IL-2, and their incidence decreased over time. No new serious treatment-related AEs were reported after 6 months post-lifileucel infusion. Characteristics of long-term responders and patterns of response will be presented.

Conclusions This 4-year analysis represents the longest follow-up to date of patients treated with lifileucel TIL cell therapy in the post-ICI setting. In heavily pretreated patients with advanced melanoma, one-time lifileucel TIL cell therapy demonstrated a 4-year OS rate of 22.2%, and 20.8% of responses were ongoing ≥4 years. These promising results continue to show favorable survival outcomes, durable responses, and no long-term safety concerns, supporting the use of lifileucel as a potential treatment option in these patients.

Acknowledgements Under the direction of the authors, Amanda Kelly (Iovance Biotherapeutics, Inc) provided medical writing support and Ashley Wirsing (Peloton Advantage, LLC, an OPEN Health company) provided graphics support.

Trial Registration NCT02360579

Ethics Approval The study was approved by the institutional review board at each site and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines of the International Conference on Harmonization. All patients provided written informed consent.

Abstract 776 Figure 1

Time to response, duration of response, and time on efficacy assessment for confirmed responders (PR or better)

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