844P Efficacy and safety of lifileucel, an investigational autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma previously treated with anti-LAG3 antibody

Abstract

Lifileucel showed durable responses in patients (pts) with advanced (unresectable/metastatic) melanoma in the post anti–PD-1 setting, with an ORR of 36% (Sarnaik JCO 2021). The recent approval of relatlimab (anti–LAG3 antibody) + nivolumab provides a new option for first-line (1L) treatment of advanced melanoma; however, ORR after exposure to this novel combination has been reported only for anti–CTLA-4–based therapies (11%; Menzies NEJM 2022). In the phase 2, C-144-01 study (NCT02360579), pts with advanced melanoma were previously treated with immune checkpoint inhibitor(s) (ICI) and BRAF ± MEK inhibitors (if BRAF V600 mutation-positive). We performed a retrospective exploratory analysis to assess efficacy and safety of lifileucel in pts enrolled in C-144-01 who progressed on/after anti-LAG3–containing therapy. ORR was assessed by investigators per RECIST v1.1. Thirteen pts received prior anti-LAG3 (12 with anti–PD-1; 1 with anti–PD-1 + anti–CTLA-4), with a median of 3 prior therapies. Anti-LAG3 was the last therapy prior to TIL therapy in 7 pts; 6 pts had other therapies after anti-LAG3 (eg, chemotherapy, ICI, targeted therapy). Anti-LAG3 was used in 1L in 4 pts; 9 pts received it post-progression. Median duration of anti-LAG3 therapy was 3.3 mo (range, 0.03–9.2 mo). ORR for lifileucel was 38.5% (5 partial responses); 3 responders had primary and 2 acquired resistance to anti-LAG3 + anti–PD-1. Responses were durable, with 60% of responses extending beyond 12 mo. Safety profile was consistent with prior reports; most common (≥30%) grade 3/4 treatment-emergent adverse events were anemia (85%), thrombocytopenia (85%), febrile neutropenia (39%), leukopenia (31%), neutropenia (31%), and lymphopenia (31%). Lifileucel showed an encouraging 38.5% ORR in pts with advanced melanoma refractory to prior anti-LAG3 + anti–PD-1 ± anti–CTLA-4. Similar to prior observations in pts after anti–PD-1 therapy, both primary and acquired anti-LAG3–resistant pts responded to lifileucel, suggesting that lifileucel outcomes may not be affected by prior anti-LAG3 therapy.