A pilot trial of autologous tumor infiltrating lymphocytes (lifileucel, LN-144) for patients with asymptomatic melanoma brain metastases.

TPS9603 Background: Melanoma brain metastases (MBM) are a leading cause of morbidity and mortality for patients with advanced melanoma. Modern systemic therapies are insufficient at controlling MBM, resulting in median overall survival (OS) of <1 year. Adoptive T cell therapy, using tumor infiltrating lymphocytes (TIL), has demonstrated efficacy in treating advanced melanoma. Lifileucel (LN-144), an autologous TIL product, was recently shown to be safe and effective for patients with PD-1 refractory melanoma. However, no trials have yet explored lifileucel in patients with active MBM. Methods: This single-center pilot trial (NCT05640193) aims to enroll 10 pts with asymptomatic MBM from non-uveal melanoma to receive lifileucel. Patients must have ≥1 intracranial lesion measuring 5-30mm visible on MRI to be used as a target lesion for modified (m)RECIST measurement, progression on prior anti-PD-1 therapy (with or without anti-CTLA-4), progression on targeted therapy (if BRAF V600E/K-mutated), ECOG PS ≤1, ≥1 resectable lesion(s) (≥1.5 cm), recovered from prior surgery/anticancer treatment-related AEs (grade ≤1). Patients are ineligible if they have symptomatic MBM and/or require corticosteroids of ≥10 mg/day of prednisone or equivalent. Lifileucel is generated from resected tumor in a centralized GMP process. The regimen includes nonmyeloablative lymphodepletion with cyclophosphamide 750 mg/m 2 on days 1-3 and fludarabine 30 mg/kg on days 1-4 (reduced dose compared with standard lifileucel protocol), lifileucel infusion, and up to 6 doses of high-dose IL-2. The primary endpoint is feasibility, defined as ≥7/10 patients who undergo tumor resection successfully receiving lifileucel infusion. Secondary endpoints are safety, feasibility of manufacturing lifileucel in patients with MBM, and brain metastasis response rate (BMRR) per mRECIST 1.1. Exploratory endpoints include overall objective response rate by mRECIST 1.1, best extracranial response rate, intracranial progression-free survival (PFS), overall PFS, OS. Extensive correlative analyses of peripheral blood mononuclear cells, plasma, tumors, and cerebrospinal fluid are planned to better understand MBM growth, treatment resistance, and response of the central nervous system to lifileucel. Clinical trial information: NCT05640193 .