Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study

  • J Immunother Cancer. 2022 Dec;10(12):e005755. doi: 10.1136/jitc-2022-005755.
Jason Chesney  1 ,  Karl D Lewis  2 ,  Harriet Kluger  3 ,  Omid Hamid  4 ,  Eric Whitman  5 ,  Sajeve Thomas  6 ,  Martin Wermke  7 ,  Mike Cusnir  8 ,  Evidio Domingo-Musibay  9 ,  Giao Q Phan  10 ,  John M Kirkwood  11 ,  Jessica C Hassel  12 ,  Marlana Orloff  13 ,  James Larkin  14 ,  Jeffrey Weber  15 ,  Andrew J S Furness  14 ,  Nikhil I Khushalani  16 ,  Theresa Medina  2 ,  Michael E Egger  1 ,  Friedrich Graf Finckenstein  17 ,  Madan Jagasia  17 ,  Parameswaran Hari  17 ,  Giri Sulur  17 ,  Wen Shi  17 ,  Xiao Wu  17 ,  Amod Sarnaik  18
Affiliations
  • 1. Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
  • 2. Medical Oncology, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, USA.
  • 3. Medical Oncology, Hematology & Oncology, Melanoma and Onco-Dermatology, Genitourinary Oncology, Yale New Haven Health Smilow Cancer Hospital, New Haven, Connecticut, USA.
  • 4. Hematology Oncology, The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, California, USA.
  • 5. Atlantic Health System Cancer Care, Morristown, New Jersey, USA.
  • 6. Hematology and Oncology, Orlando Health Cancer Institute, Orlando, Florida, USA.
  • 7. Technische Universität Dresden - NCT/UCC Early Clinical Trial Unit, Dresden, Sachsen, Germany.
  • 8. Division of Hematology & Oncology, Mount Sinai Medical Center, Miami Beach, Florida, USA.
  • 9. Division of Hematology, Oncology and Transplantation, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
  • 10. Surgery, Virginia Commonwealth University, Massey Cancer Center, Richmond, Virginia, USA.
  • 11. Medicine, Dermatology and Translational Science, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • 12. Skin Cancer Center, Universität Heidelberg, Heidelberg, Baden-Württemberg, Germany.
  • 13. Thomas Jefferson University Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania, USA.
  • 14. The Royal Marsden NHS Foundation Trust, London, UK.
  • 15. Department of Medicine, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA.
  • 16. Department of Cutaneous Oncology, H Lee Moffitt Cancer Center, Tampa, Florida, USA.
  • 17. Iovance Biotherapeutics Inc, San Carlos, California, USA.
  • 18. Department of Cutaneous Oncology, H Lee Moffitt Cancer Center, Tampa, Florida, USA [email protected].
PMID: 36600653 DOI: 10.1136/jitc-2022-005755
Abstract

Background: Patients with advanced Melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in Melanoma.

Methods: Eligible patients had advanced Melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1).

Results: The Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; Lactate Dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%).

Conclusions: Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced Melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease.

Keywords
Clinical Trials, Phase II as Topic; Immunotherapy; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Melanoma.