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789 Lifileucel TIL cell monotherapy in patients with advanced melanoma after progression on immune checkpoint inhibitors (ICI) and targeted therapy: pooled analysis of consecutive cohorts (C-144–01 study)
  1. Amod Sarnaik1,
  2. Karl Lewis2,
  3. Harriet Kluger3,
  4. Omid Hamid4,
  5. Eric Whitman5,
  6. Sajeve Thomas6,
  7. Martin Wermke7,
  8. Mike Cusnir8,
  9. Evidio Domingo-Musibay9,
  10. Giao Phan10,
  11. John Kirkwood11,
  12. Jessica Hassel12,
  13. Marlana Orloff13,
  14. James Larkin14,
  15. Jeffrey Weber15,
  16. Andrew Furness14,
  17. Nikhil Khushalani1,
  18. Theresa Medina2,
  19. Friedrich Finckenstein16,
  20. Madan Jagasia16,
  21. Parameswaran Hari16,
  22. Giri Sulur16,
  23. Wen Shi16,
  24. Xiao Wu16 and
  25. Jason Chesney17
  1. 1H. Lee Moffitt Cancer Center, Tampa, FL, USA
  2. 2University of Colorado Cancer Center-Anschutz Medical Campus, Aurora, CO, USA
  3. 3Yale School of Medicine and Smilow Cancer Center, Yale New Haven Hospital, New Haven, CT, USA
  4. 4The Angeles Clinic and Research Institute, a Cedars Sinai Affiliate, Los Angeles, CA, USA
  5. 5Atlantic Health System Cancer Care, Morristown, NJ, USA
  6. 6Orlando Health Cancer Institute, Orlando, FL, USA
  7. 7Technical University Dresden, NCT/UCC Early Clinical Trial Unit, Dresden, Germany
  8. 8Mount Sinai Medical Center, Miami Beach, FL, USA
  9. 9University of Minnesota, Masonic Cancer Center, Minneapolis, MN, USA
  10. 10Virginia Commonwealth University, Massey Cancer Center, Richmond, VA, USA
  11. 11UPMC Hillman Cancer Center, Pittsburgh, PA, USA
  12. 12Skin Cancer Center, University Hospital Heidelberg, Heidelberg, Germany
  13. 13Thomas Jefferson University, Sidney Kimmel Cancer Center, Philadelphia, PA, USA
  14. 14The Royal Marsden Hospital NHS Foundation Trust, London, UK
  15. 15Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, USA
  16. 16Iovance Biotherapeutics, Inc., San Carlos, CA, USA
  17. 17UofL Health – Brown Cancer Center, University of Louisville, Louisville, KY, USA


Background Despite improved outcomes in advanced (unresectable or metastatic) melanoma, many patients progress after ICI,1-3 and have low response rates to subsequent therapy.4-7 Lifileucel, a one-time autologous TIL cell therapy, demonstrated an investigator-assessed ORR of 36% in Cohort 2 (C2), which enrolled 66 patients who progressed post-ICI and appropriate targeted therapy.8,9 We now report outcomes of 153 patients enrolled across C2 and C4 (NCT02360579), representing the largest phase 2 study of cell therapy in melanoma.

Methods Eligibility criteria were identical for C2 and C4. Patients had ≥1 lesion(s) resected (~1.5 cm in diameter postresection) and shipped to a central GMP facility for 22-day lifileucel manufacturing. All patients received a nonmyeloablative lymphodepletion (NMA-LD) regimen, a single lifileucel infusion, and up to 6 doses of high-dose IL-2. Primary endpoint was IRC-assessed ORR (RECIST v1.1).

Results The full analysis set included 153 patients (C2: n=66; C4: n=87) treated with lifileucel, with a median of 3 prior lines of therapy (range: 1-9) and substantial baseline disease burden (>3 target and non-target lesions: 76%; median target lesion SOD: 97.8 mm; LDH >ULN: 54%). ORR was 31% (95% CI: 24.1%-39.4%) (C2: 35%; C4: 29%), with 8 CRs and 40 PRs (figure 1). At median study follow-up of 27.6 months, median DOR was not reached (NR). Forty-two percent of responses extended ≥18 months, and 40% (19/48) of responses were ongoing at time of datacut (figure 2). In multivariable analyses adjusted for ECOG PS, elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); normal LDH and SOD < median were associated with higher odds of response than either (OR=2.08) or both (OR=4.42) risk factors. The median OS was 13.9 months (95% CI: 10.6-17.8. In an analysis of survival by response at first assessment (1.5 months post-lifileucel infusion), median OS in responders was NR (95% CI: 22.5 months-NR). The most common (≥30%) G3/4 TEAEs were thrombocytopenia (77%), anemia (50%), and febrile neutropenia (42%). TEAEs were consistent with known safety profiles of NMA-LD and IL-2, and their incidence decreased within the first 2 weeks post-lifeucel infusion, characteristic of one-time treatment.

Conclusions Lifileucel demonstrated clinically meaningful and durable activity (ORR: 31%; mDOR: NR) in heavily pretreated patients with advanced melanoma and high tumor burden after ICI (and targeted therapy, where appropriate). Favorable safety profile and sustained responses support the potential benefit of one-time lifileucel TIL cell therapy as a novel treatment option for patients without approved therapies post-ICI.

Acknowledgements Medical writing support was provided by Second City Science, with funding from Iovance Biotherapeutics.

Trial Registration NCT02360579


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  8. Sarnaik AA, Hamid O, Khushalani NI, et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J Clin Oncol. 2021;39:2656–2666.

  9. Larkin J, Sarnaik A, Chesney JA, et al. Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti–PD-1 therapy. J Clin Oncol. 2021;39(suppl 15):abstract 9505.

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 Harmonisation. All patients provided written informed consent.

Abstract 789 Figure 1

Best percentage change from baseline in target lesion SOD

Abstract 789 Figure 2

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

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