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. 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.
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).
Notably, patient T06 (42-year-old male), who had received two prior lines of therapy and experienced grade 2 CRS after TAEST16001 treatment, exhibited a partial response of upper arm and multiple lung metastatic lesions after 4 weeks of cell infusion, maintaining more than 14 months following treatment . As the lung metastatic lesions remained a great partial response even at the time of progression, the patient underwent surgical resection of a lesion in the upper arm. Another patient, T02 (27-year-old male), who had recurrent myxoid liposarcoma in the right leg after receiving five surgeries, also exhibited a partial response and sustained more than 1 year following treatment.
In 2024, the American Society of Clinical Oncology (ASCO) reported phase IIA study of high-affinity TCR-T (TAEST16001) targeting NY-ESO-1 in soft tissue sarcoma（NCT05549921）.
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/m2/day). TAEST16001 cells were administered at 1.2 × 1010± 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 × 1010 was 54.5% (6/11).
At present, there are still many clinical trials of new anti-cancer technologies in China seeking patients. Consultation on new drugs and technologies, you can contact Beijing South Region Oncology Hospital International Department.
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REFERENCES
1.https://www.xphcn.com/xiangxue/index_33.aspx
2.https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.11502
3.https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(23)00261-6
4.https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.11548
Post time: Dec-18-2024