Phase IIA study of high-affinity TCR-T (TAEST16001) targeting NY-ESO-1 in soft tissue sarcoma.

11548 Background: TAEST16001 cells are genetically engineered autologous T cells expressing high-affinity NY-ESO-1-specific T-cell receptor (TCR) targeting NY-ESO-1 (expressed in a wide range of tumors) positive soft tissue sarcoma (STS) in the context of HLA-A*02:01. A phase I study of in patients with advanced STS (NCT04318964) demonstrated safety and preliminary indication of efficacy at ASCO 2022. Here, we will present our encouraging phase IIa results. Methods: This is an open-labeled, single arm study to evaluate efficacy and safety of TAEST16001 cells in patients with advanced STS (NCT05549921). Enrolled patients underwent apheresis, their isolated T cells expanded in vitro after transduction with a lentiviral vector expressing high affinity NY-ESO-1 TCR. Patients received 3-day lymphodepleting chemotherapy (cyclophosphamide 15 mg/kg/day and fludarabine 20 mg/m 2 /day). TAEST16001 cells were administered at 1.2 × 10 10 ± 30% cells (determined through our phase I data) and they also received 14-day IL-2 s.c. injection. Target efficacy ( per RECIST 1.1) was set at overall response rate (ORR) =25% for the first stage cohort of 12 patients. Results: As of January 2024, 8 patients were enrolled (M:F 4: 4; mean age: 40 yrs.; median prior regimens: 3 (range:2-5)). TAEST16001 cells demonstrated a manageable safety profile consistent with previous phase I study. The common (n>1) reported grade (G) 3 adverse events were lymphocytopenia (n=8), decreased WBC count (n=7), neutropenia (n=6), elevated γ-GT (n=3), hypokalemia (n=2). Six patients had cytokine release syndrome (CRS) (G3: 1; G2: 1; G1: 4), and 2 patients also experienced G1 ICANS, all resolved completely after symptomatic treatment. Importantly, after at least two tumor assessments, 4 had confirmed partial response, 3 had stable disease, and 1 had progressive disease. The ORR at cut-off date was 50%. The median time to initial response was 1.1 months (1.1 to 2.2) and median duration of response was 5.0 months (1.5 to 8.8). Most patients are still being follow-up. When pooling the data for the same dose in phase I part, ORR at dose of 1.2 × 10 10 was 54.5% (6/11). Conclusions: TAEST16001 demonstrated an acceptable safety profile. The encouraging efficacy data (ORR=50%) exceeded our pre-specified target efficacy (ORR=25%). The review committee has recommended TAEST16001 to proceed early to the next stage of clinical development. Clinical trial information: NCT05549921 .