Lifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study.

9515 Background: Lifileucel is a personalized, one-time tumor-derived autologous T-cell immunotherapy approved for the treatment of adult patients (pts) with advanced (unresectable or metastatic) melanoma previously treated with a programmed cell death-1 (PD-1)–blocking antibody, and, if BRAF V600 mutation–positive, a BRAF inhibitor with or without a MEK inhibitor. In the registrational C-144-01 study (NCT02360579), pts with advanced melanoma who received lifileucel had an objective response rate (ORR) of 31.4%. Follow-up in therapeutic trials targeting refractory patients with refractory melanoma typically span months rather than years due to lack of activity. Reflective of the durability of lifileucel, we nowreport 5-year survival outcomes from the C-144-01 study. Methods: C-144-01 (NCT02360579) is a phase 2, multicenter, multicohort, open-label study of lifileucel. Eligible pts had advanced melanoma that had progressed on or after immune checkpoint inhibitor and targeted therapy, where appropriate. Before lifileucel infusion, pts underwent nonmyeloablative lymphodepletion (NMA-LD; cyclophosphamide, 60 mg/kg × 2 d plus fludarabine 25 mg/m 2 × 5 d). Pts received cryopreserved lifileucel followed by up to 6 doses of interleukin-2 (IL-2; 600,000 IU/kg every 8–12 hours). The primary endpoint was ORR assessed by an independent review committee (IRC) using RECIST v1.1. Key secondary endpoints were duration of response (DOR), overall survival (OS), and safety. Results: Among pts who received lifileucel (n = 153; median age, 56 y; range, 20–79), 54% were male. All pts had an Eastern Cooperative Oncology Group Performance Status of 0 or 1 and previously received anti–PD-1/PD-L1 therapy. Pts had a median of 3 prior lines of therapy (range, 1–9) and 55% were primary refractory to anti–PD-1/PD-L1 therapy. At a median follow-up of 57.8 mo, all pts have completed or discontinued the study, with 28 (18.3%) pts having completed the 5-year study follow-up. The ORR was 31.4% (complete response, 5.9%; partial response, 25.5%). Median DOR was 36.5 mo (95% confidence interval [CI]: 8.3–not reached), with 31.3% of responders completing the 5-year assessment with a sustained response. Median time to best response was 1.5 mo (range, 1.3–30.4). Median OS was 13.9 mo (95% CI: 10.6–17.8); the 5-year OS rate was 19.7% (95% CI: 13.3–27.0). Treatment-emergent adverse events were consistent with known safety profiles of NMA-LD and IL-2. The extended follow-up revealed no new safety signals. Conclusions: This 5-year analysis of the C-144-01 trial is the longest follow-up of the largest group of pts with melanoma treated with tumor-infiltrating lymphocytes in a single study. This study illustrates lifileucel’s continued durability of response and survival benefit up to 5 years after a single administration without any long-term safety concerns. Clinical trial information: NCT02360579 .