Armored TIL GT201 induces potent tumor-specific TCR expansion and durable antitumor responses in advanced solid tumor

Background: Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated activity in solid tumors but remains constrained by T-cell exhaustion and an immunosuppressive tumor microenvironment. GT201 is an engineered, cytokine-armored TIL product expressing membrane-bound IL-15 (mbIL-15) designed to enhance TIL persistence and antitumor function. A multi-center, open-label, single-arm exploratory clinical study was initiated to evaluate the safety, tolerability, and preliminary efficacy of GT201 in patients with advanced solid tumor. Method: The primary endpoint was to evaluate the tolerance and safety profile according to CTCAE v5.0. Secondary endpoints included preliminary efficacy measures such as overall response rate (ORR), disease control rate (DCR), assessed per RECIST v1.1, as well as pharmacokinetics of GT201. Exploratory endpoint included longitudinal tumor biopsies and peripheral blood sampling, analyzed by single-cell RNA/TCR sequencing and bulk TCR sequencing to track clonal dynamics and identify tumor-specific TCRs. Result: As of November 4, 2025, twelve patients were enrolled (median age 52.5 years; median of two prior lines of therapy). GT201 demonstrated a favorable safety profile: most AEs were Grade 1-2, while Grade ≥3 events were attributable to lymphodepleting chemotherapy or IL-2 support and resolved within 14 days. Preliminary efficacy signals were encouraging, with an ORR of 58.3% (7/12) and a DCR of 83.3% (10/12), including two complete responses (16.7%) and five partial responses (41.7%). Correlative multi-omics profiling revealed that mbIL-15-expressing cells were enriched in post-infusion tumor samples, and their corresponding TCRs underwent marked clonal expansion. A putative tumor-specific T-cell subset (4-1BB⁺CD8⁺ with high effector/exhaustion and low stemness signatures in tumor samples pre- and post-infusion) was preferentially expanded during manufacturing and showed a pronounced expansion peak in peripheral blood between Days 7-28 in responders. This subset was scarce at baseline and exhibited minimal expansion in non-responders. In contrast, “TIL-only” TCRs, which were clonotypes present in the infused product but absent pre-infusion, did not expand in peripheral blood in any patient. Conclusion: GT201 exhibited a manageable safety profile and encouraging early efficacy in patients with advanced solid tumor, with ongoing enrollment to further inform clinical outcomes. Integrated multi-omics analyses indicate that expansion of tumor-specific TCRs, during both manufacturing and post-infusion in responding patients, correlates more strongly with clinical benefit than expansion of TIL-only TCRs. Continued longitudinal sampling and functional validation of putative tumor-specific clonotypes will be essential to establish their utility as biomarkers of response in GT201 therapy.