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NY-ESO-1 TCR T-Cell Therapy Shows Clinical Activity in Soft Tissue Sarcoma

Overall response rate was 41.7% and median progression free survival was 7.2 months.

The NY-ESO-1–specific T-cell receptor (TCR) T-cell therapy TAEST16001 has demonstrated promising clinical activity in advanced soft tissues sarcoma with an acceptable safety profile, according to data from a phase 1 study (NCT04318964).

These data were presented at the 2022 American Society of Clinical Oncology (ASCO) meeting, held June 3-7, 2022, held both virtually and in Chicago, Illinois by Xing Zhang, MD, professor and chief physician, department of Immunotherapy and Medical Oncology of Melanoma and Sarcoma, Sun Yat-sen University Cancer Center.

“The molecular target of the TCR therapy is NY-ESO-01, a cancer testis antigen. TAEST16001 is a TCR-affinity enhanced specific T-cell therapy and expresses an engineered high affinity NY-ESO-01 TCR,” Zhang said during her presentation.

Apheresed T cells were transduced with a lentiviral vector containing NY-ESO-1 TCR and expanded in vitro. Patients received cyclophosphamide (15 mg/kg/day for 3 days) and fludarabine (20 mg/m2/day for 3 days lymphodepleting chemotherapy before TAEST16001 cell infusion. TAEST16001 cells were administered at 4 dose levels (DLs): 5 × 108± 30%, 2 × 109± 30%, 5 × 109± 30%, and 1.2 × 1010± 30%, and patients received interleukin-2 subcutaneous injection for 14 days after infusion.

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Twelve patients with advanced soft tissue sarcoma have been enrolled, 3 each in the 4 cohorts, as of December 31, 2021. Seven participants were male and median age was 37.9 years. Participants had a median of 2 prior treatment regimens (range, 1-3).

Overall, 5 patients had a partial response (PR), 5 had stable disease (SD), and 2 had progressive disease (PD) for an overall response rate (ORR) of 41.7%. By cohort, DL1 and DL4 had a 66.7% ORR, DL2 had a 33.3% ORR, and DL3 had a 0% ORR, with 2 PDs and 1 SD. Median time to response was 1.9 months (range, 0.9 to 3.0), and median duration of response was 14.1 months (range, 5.0 to 14.2). Median progression free survival was 7.2 months (95% CI, 2.6-11.7).

TAEST16001 was well-tolerated with no dose-limiting toxicities observed. Grade 3 adverse events (AEs) included lymphopenia (n = 12), leukopenia (n = 10), neutropenia (n = 11), anemia (n = 4), thrombocytopenia (n = 1), hypokalemia (n = 1), and fever (n = 1). Two cases of grade 2 cytokine release syndrome resolved after symptomatic treatment. Investigators did not observe any neurotoxicity or serious AEs related to treatment and maximum tolerated dose (MTD) was not reached. Pharmacokinetic modeling revealed peak expansion of TAEST16001 cells was 6.23 days after infusion, and there was no relationship between clinical response and Cmax/AUC0-28.

“TAEST16001 cells showed an acceptable safety profile, and MTD was not reached. A single TAEST16001 cell infusion resulted in durable tumor responses in a subset of patients with soft tissue sarcoma, encouraging PFS, ORR, and duration of response. A phase 2 study is encouraged due to emerging efficacy data in the phase 1 trial,” Zhang concluded.

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Zhang X, Weng D, Pan Q, et al. 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. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #11502.