Phase I clinical trial to assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of NY-ESO-1–specific TCR T-cells (TAEST16001) in HLA-A*02:01 patients with advanced soft tissue sarcoma.

11502 Background: NY-ESO-1 is a cancer/testis antigen with expression in a wide range of tumor types. TAEST16001 cells are genetically engineered autologous T cells that express high-affinity NY-ESO-1-specific T-cell receptor (TCR) targeting NY-ESO-1+ soft tissue sarcoma in the context of HLA-A*02:01. Here, we report preliminary results of TAEST16001 cells from an ongoing, dose-escalation and expansion study in HLA-A*02:01 positive patients with advanced soft tissue sarcoma expressing NY-ESO-1 antigen. Methods: This is an open, single arm, dose-escalation and expansion study to evaluate safety, tolerability, PK, PD and preliminary efficacy of TAEST16001 cells in patients with soft tissue sarcoma. Enrolled patients underwent apheresis, and their isolated T cells were expanded in vitro after transducing with a lentiviral vector containing NY-ESO-1 TCR. Prior to TAEST16001 cells infusion, patients were to receive lymphodepleting chemotherapy consisting of cyclophosphamide (15 mg/kg/day ´ 3 days) and fludarabine (20 mg/m2/day ´ 3 days). TAEST16001 cells were administered at 5 × 108 ± 30% (dose level 1), 2 × 109 ± 30% (dose level 2), 5 × 109 ± 30% (dose level 3) and 1.2 × 1010 ± 30% (dose level 4/expansion) transduced cells. After TAEST16001 cells infusion, patients were to receive interleukin-2 subcutaneous injection for 14 days. Tumor responses were assessed by RECIST/iRECIST. Results: As of 31 December 2021, 12 patients with advanced soft tissue sarcoma were enrolled (M:F 7:5; mean age = 37.9; median prior regimens = 2 (range 1-3)). TAEST16001 cells were well-tolerated with no dose limiting toxicity. The most frequently reported grade ³ 3 adverse events were lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), anemia (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), and fever (n = 1). Two patients presented with cytokine release syndrome (grades 2) and resolved after symptomatic treatment. None of the patients had neurotoxicity, or serious adverse events related to cell infusion. The maximum tolerated dose (MTD) was not reached. PK modelling indicated that Tmax of TAEST16001 cells were 6.23 days after cells infusion, and there were no relationship between clinical response and Cmax/AUC0-28. Among 12 efficacy-evaluable patients, 5 patients had a partial response, 5 patients had stable disease, and 2 patients had progressive disease. The overall response rate was 41.7%. The median time to an initial response was 1.9 month (range, 0.9 to 3.0), and the median duration of response was 14.1 months (range, 5.0 to 14.2). Conclusions: TAEST16001 cells showed an acceptable tolerability profile overall. MTD was not reached. Emerging efficacy data encouraged the continued expansion study of TAEST16001 cells in advanced soft tissue sarcoma. Clinical trial information: NCT04318964.