Abstract LB414: Updated clinical efficacy and translational biomarker analysis of tumor infiltrating lymphocyte therapy (LM103) in metastatic melanoma

Abstract Background: Tumor-infiltrating lymphocytes (TIL) adoptive therapy has shown clinical efficacy for metastatic melanoma refractory to anti-PD-1 therapy. This phase I clinical trial evaluated the safety and efficacy of TILs (LM103) in advanced Chinese patients (pts) with melanoma, and explored correlative biomarkers. Methods: Pts with metastatic melanoma progressing on standard therapies, had both resectable and measurable tumors were eligible to be enrolled. Pts received a lymphodepletion regimen before the intravenous autologous LM103 infusion and then high dose IL-2 for 6 doses (200000IU/Kg, 1 dose per day) to support T cell survival and proliferation. Primary endpoint was safety; secondary endpoints included efficacy and translational analysis. Results: Fourteen pts (4 males; aged 26-70 yrs) were enrolled: 5 acral, 4 cutaneous, 4 mucosal, and 1 unknown primary. Infused autologous TIL contained 3.58-19.47x10^10 viable cells. The most frequent treatment-emergent adverse events (TEAEs) were myelosuppression (100%), fever (85.7%), rash (71.4%), and alopecia (71.4%). Grade 3-4 TEAEs included leukopenia (85.7%), neutropenia (78.6%), lymphopenia (78.6%), fever (71.4%), thrombocytopenia (57.1%), and anemia (28.6%). The ORR and DCR per RECIST v1.1 were 35.7% and 85.7%, respectively. With a median follow-up of 5.51 months, the median PFS and OS were 4.52 months (95% CI, 2.07 to 14.31) and 16.58 months (95% CI, 5.16 to NA), respectively. Immunofluorescence analysis and whole-exome sequencing for the baseline tumors did not reveal any significant difference in the infiltration of multiple immune cell populations and tumor mutation burden, respectively, between responders (Rs) and non-responders (NRs). T cell receptor-sequencing (TCR-seq), flow cytometry analysis and ELISA were performed for the TIL infusion products and the peripheral blood of patients at various time points before and after infusion. The frequency of shared T cell clones between TIL infusion products and post-infusion peripheral blood maintained >60% till 6 month after infusion, indicating that LM103 TILs persisted well in vivo. The frequencies of dominant T cell clones of infused TILs were higher in Rs than in NRs, implying a correlation between TILs persistence and clinical outcome. In addition, the IFN-γ level in the peripheral blood at Week 6 of NRs was significantly higher than that of Rs while other cytokine (such as TNF-α, IL-2, TGF-β1 etc) levels were similar between these two groups. Percentage of CD3+, CD4+ or CD8+ T cells in the peripheral blood was also not significantly different between R and NRs. Conclusion: LM103 TIL therapy demonstrated manageable safety and encouraging efficacy in treatment-refractory melanoma. Clinical response correlated with the persistence and expansion of infused TIL clones, instead of baseline tumour features. Trial registration number: CTR20233999. Citation Format: Chuanliang Cui, Li Zhou, Yan Kong, Xuan Wang, Yue Yang, Jiayong Liu, Zhichao Tan, Zhihong Chi, Lu Si, Bin Lian, Lili Mao, Hui Tian, Yuan Yuan, Yongming Xue, Jun Guo. Updated clinical efficacy and translational biomarker analysis of tumor infiltrating lymphocyte therapy (LM103) in metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB414.