119O Long-term efficacy and patterns of response of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: A 4-year analysis of the C-144-01 study
Theresa Medina, Jason Chesney, Eric D. Whitman, Harriet M. Kluger, Sajeve Thomas, Amod Sarnaik, John M. Kirkwood, James Larkin, Jeffrey S. Weber, Omid Hamid, Martin Wermke, Friedrich Graf Finckenstein, Jeffrey Chou, Brian Gastman, G. Sulur, Xiao Wu, Wen Shi, E. Domingo-Musibay
Abstract
The large proportion of patients (pts) with advanced (unresectable or metastatic) melanoma resistant to immune checkpoint inhibitors (ICI) define a significant unmet need. Lifileucel, a one-time autologous TIL cell therapy, has demonstrated durable clinical benefit in this setting, with the C-144-01 study showing an ORR of 31.4% in a heavily pre-treated population. We report 4-year follow-up data from C-144-01 on lifileucel’s treatment outcomes and patterns of response. C-144-01 (NCT02360579) is a prospective, open-label, multicohort, nonrandomized phase 2 study; data from pts in Cohorts 2 and 4 are presented. Pts had ≥1 lesion(s) resected (≥1.5 cm diameter) for 22-day cryopreserved lifileucel manufacturing. The treatment regimen consisted of nonmyeloablative lymphodepletion (cyclophosphamide 60 mg/kg/d × 2d, fludarabine 25 mg/m2/d × 5d), followed by a single lifileucel infusion and ≤6 doses of high-dose IL-2 (600,000 IU/kg). As of data cutoff (30 June 2023), 153 pts were assessed; median study follow-up was 48.1 months. Independent review committee-assessed ORR by RECIST v1.1 was 31.4% with median DOR (months) of NR. The 1-, 2-, 3-, and 4-year OS rate was 54.0%, 33.9%, 28.4%, and 21.9%, respectively. Responders (n=48) had a median age of 55.0 years with median of 3 prior lines of therapies. Clinically meaningful 4-year OS rates were seen across all patterns of response (range, 37.2%–68.2%; Table); pts with deepened response had numerically higher OS rate. Treatment-emergent adverse events were consistent with known safety profiles of lymphodepletion and IL-2.Table 119O:OS and DOR by patterns of responseEarly respondersa (n=39)Late respondersb (n=9)Responders with deepened responsec (n=16)Responders without deepened response (n=32)All responders (n=48)OS rate at 4 y, % (95% CI)48.3 (31.9, 62.9)41.7 (10.9, 70.8)68.2 (39.5, 85.4)37.2 (21.0, 53.5)47.3 (32.5, 60.7)Median DOR, mo (95% CI)NR (6.1, NR)19.8 (4.1, NR)NR (8.3, NR)26.2 (4.1, NR)NR (8.3, NR)aPatients with CR or PR on Day 42 visit. bPatients with CR or PR after Day 42 visit. cPatients who had SD and improved to confirmed PR or had PR and improved to confirmed CR. CI, confidence interval; CR, complete response; DOR, duration of response; OS, overall survival; PR, partial response; SD, stable disease. Open table in a new tab aPatients with CR or PR on Day 42 visit. bPatients with CR or PR after Day 42 visit. cPatients who had SD and improved to confirmed PR or had PR and improved to confirmed CR. CI, confidence interval; CR, complete response; DOR, duration of response; OS, overall survival; PR, partial response; SD, stable disease. In this 4-year analysis of heavily pretreated pts with advanced melanoma, treatment with lifileucel produced durable efficacy, leading to long-term survival benefit across different patterns of responders.