Abstract Purpose: Recurrent ovarian cancer (rOC) remains an unmet need. This first-in-human phase 1 trial evaluated GC203, an autologous tumor-infiltrating lymphocyte (TIL) product genetically modified via piggyBac transposon to overcome the immunosuppressive tumor microenvironment (TME). Patients and Methods: A cohort of 18 patients with rOC who were heavily pretreated (median, 3.5 prior lines of therapy) underwent lymphodepletion with cyclophosphamide and hydroxychloroquine, followed by GC203 infusion. The primary endpoints were safety and tolerability. Secondary endpoints, assessed in the full analysis set (FAS) using RECIST 1.1 guidelines, encompassed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Exploratory analyses included the Morisita Overlap Index (MOI) to quantify T cell receptor (TCR) repertoire similarity between infused TILs and circulating T cells. Results: The GC203 regimen demonstrated a favorable safety profile. Treatment-related adverse events were primarily hematological, with grade≥3 lymphopenia and neutropenia each occurring in 57% of patients. All proved to be transient with a median resolution 7 days. The regimen achieved an unconfirmed ORR of 33.3% (6/18 patients) alongside a disease control rate (DCR) of 83.3%. Survival analyses revealed a median PFS of 7.2 months (95% CI: 1.0-13.4) and a median OS of 17.1 months (95% CI: 9.5-24.7). A key exploratory analysis identified the MOI as a significant predictor of treatment response, achieving an area under the curve (AUC) of 0.79. Conclusion: The GC203 regimen, combining piggyBac-mbIL-7 autologous TILs with anti-PD-1 antibody, demonstrates favorable safety and promising efficacy in heavily pretreated rOC, which supports its further development in this high-need population.
Guo et al. (Tue,) studied this question.