PiggyBac-Engineered Membrane-Bound IL7 TILs Combined with Anti-PD-1 Antibody Demonstrates Efficacy in Recurrent Ovarian Cancer: A First-in-Human Phase I Trial.

PURPOSE: Recurrent ovarian cancer (rOC) remains an unmet need. This first-in-human phase I trial evaluated GC203, an autologous tumor-infiltrating lymphocyte (TIL) product genetically modified via piggyBac transposon to overcome the immunosuppressive tumor microenvironment.

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 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 repertoire similarity between infused TILs and circulating T cells.

RESULTS

The GC203 regimen demonstrated a favorable safety profile. Treatment-related adverse events were primarily hematologic, with grade ≥ 3 lymphopenia and neutropenia each occurring in 57% of patients. All proved to be transient with a median resolution of 7 days. The regimen achieved an unconfirmed ORR of 33.3% (6/18 patients) alongside a disease control rate of 83.3%. Survival analyses revealed a median PFS of 7.2 months [95% confidence interval (CI), 1-13.4] 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 of 0.79.

CONCLUSIONS

The GC203 regimen, combining piggyBac membrane-bound IL7 autologous TILs with anti-PD-1 antibody, demonstrates favorable safety and promising efficacy in heavily pretreated patients with rOC, which supports its further development in this high-need population.