Fast-manufactured, low IL-2-dependent FAST-TIL for the treatment of advanced melanoma in asian patients: Median 6-month follow-up data from a phase I clinical trial

Background: FAST-TIL (HS-IT101) is an innovative autologous tumor-infiltrating lymphocyte (TIL) therapy product developed using a fully enclosed, automated platform. It features minimal dependence on IL-2, requires very small amounts of starting tumor tissue (<0.05 g), and completes manufacturing in only 14 days. The Phase I clinical trial of FAST-TIL (HS-IT101) in patients with advanced solid tumors, including melanoma (NCT06342336), is ongoing, and we report preliminary clinical data with a median follow-up of 6 months. Methods: This is a Phase I, open-label, single-arm, multicenter clinical trial evaluating autologous FAST-TIL (HS-IT101) in patients with advanced melanoma who have progressed on or are intolerant to prior systemic therapy. The primary endpoint is safety, assessed by the incidence and severity of adverse events according to CTCAE v5.0. Secondary endpoints include preliminary efficacy measures and pharmacokinetic. Results: As of August 2025, 12 patients with advanced melanoma (2 cutaneous, 8 acral, and 2 mucosal) had received FAST-TIL (HS-IT101) treatment, with a median age of 60.5 years. Eleven patients had previously progressed on or were resistant to immune checkpoint inhibitor (ICI) therapy. Lymphodepletion regimens included LD-NMA conditioning (n=2: cyclophosphamide 300 mg/m² qd and fludarabine 30 mg/m² qd on Days -5 to -3) and MD-NMA conditioning (n=10: cyclophosphamide 750 mg/m² qd on Days -4 to -2, and fludarabine 30 mg/m² qd on Days -4 to -1). Following TIL infusion, patients received subcutaneous interleukin-2 (IL-2) at 2 MIU/m² once daily for 3 days. Most adverse events (AEs) were attributable to the lymphodepleting chemotherapy and IL-2 administration. No grade 4 or 5 AEs were observed, and all AEs resolved promptly with supportive care and minimal complications. Cytokine release syndrome (CRS) of grade ≤2 occurred in 5 patients (41.7%). No cases of tumor lysis syndrome (TLS) or immune effector cell-associated neurotoxicity syndrome (ICANS) were reported. In the efficacy-evaluable MD-NMA cohort (n=10), the objective response rate (ORR) was 50%, including 2 patients with confirmed complete response (CR) and 3 with confirmed partial response (PR). As of December 2025, with a median follow-up of 6 months, the median progression-free survival (mPFS) had not been reached.T-cell receptor (TCR) clonal analysis in 4 patients demonstrated robust persistence of infused T-cell clones in peripheral blood, comprising 41% to 77% of the TCR repertoire on Day 168 post-infusion. Conclusion: FAST-TIL (HS-IT101) demonstrates a favorable safety profile, promising antitumor activity, and durable clinical responses in patients with advanced melanoma. These findings support further evaluation in larger, controlled studies to confirm its therapeutic potential and establish its role in advanced melanoma treatment.