LM103, an autologous tumor-infiltrating lymphocyte monotherapy, in patients with advanced melanoma resistant to standard therapy

We conducted a phase I study to evaluate the safety, clinical activity, and immune correlates of autologous tumor-infiltrating lymphocytes (TIL) therapy LM103 in Chinese patients with refractory metastatic melanoma. Fourteen patients with refractory metastatic melanoma received lymphodepleting chemotherapy followed by LM103 infusion (3.58–19.47×10¹⁰ cells) and high-dose interleukin-2. Characteristics of baseline tumor, TIL products and pre-/post-infusion peripheral blood were analyzed. LM103 therapy demonstrated manageable safety and promising efficacy. TEAEs included myelosuppression (100%), capillary leak syndrome (100%), fever (85.7%), and rash (71.4%). Grade 3-4 TEAEs included leukopenia (85.7%), neutropenia (78.6%), lymphopenia (78.6%), fever (71.4%), and thrombocytopenia (57.1%). The objective response rate was 35.7% (95% confidence interval [CI], 12.76 to 64.86), and the disease control rate was 85.7% (95% CI, 57.19 to 98.22). Median progression-free survival was 4.52 months (95% CI, 2.07 to 14.31), and median overall survival was 16.58 months (95% CI, 5.16 to not estimable). Baseline tumor immune infiltration and mutational burden were not associated with clinical outcome. LM103 infusion induced marked peripheral T cell receptor repertoire remodeling, with more than 60% of infused TIL clones detectable in peripheral blood at 6 months. Patients with superior clinical outcomes demonstrated greater expansion and persistence of dominant TIL clones. In addition, genes favoring T cells tumor infiltration were upregulated in TILs of patients with longer PFS. LM103 showed manageable safety and encouraging antitumor activity. Clinical benefit was associated with sustained in vivo clonal persistence and upregulated genes favoring tumor re-infiltration of infused TILs. Trial registration number CTR20233999