TBI-1301 Immunotherapy Shows Improvement in Synovial Sarcoma Treatment

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Immunotherapy with TBI-1301 to target NY-ESO-1-positive tumor cells demonstrated promising results for the treatment of advanced or recurrent synovial sarcoma, according to a study published in Clinical Cancer Research. Eight patients were treated in the phase 1/2 trial (NCT03250325), and the overall response rate (ORR) was 50% (95% CI, 15.7-84.3).¹

“Overall, the results of this study generally align with those of previous studies using adoptive 358 transfer of NY-ESO-1 specific TCR engineered T cells for advanced [synovial sarcoma],” study authors wrote. “The efficacy of the treatment, in terms of [objective response rate (ORR)] and [overall survival (OS)], was strongly superior to that of pazopanib [Votrient] and in line with results of other adoptive immunotherapy regimens directed against the NY-ESO-1 antigen that have been previously reported.”¹

Patients had advanced or recurrent synovial sarcoma that could not be surgically resected and was resistant to anthracycline-based regimens. Patients were administered a split dose of 5x109 TBI-1301 intravenously for 2 days following pre-treatment cyclophosphamide, which was administered at 750 mg/m2/day for 2 days.²

The phase 1 primary end points were incidence of adverse events (AEs), appearance of replication-competent retrovirus (RCR), appearance of clonality, and blood kinetics of TBI-1301. The phase 2 primary end point was ORR. The phase 1 secondary end points were ORR, progression-free rate (PFR), OS, and progression-free survival (PFS). The phase 2 secondary end points were PFR, PFS, OS, incidence of AEs, appearance of RCR, appearance of clonality, and blood kinetics of TBI-1301.

For safety, all patients experienced AEs, and 7 of 8 patients (87.5%) had adverse drug reactions. No deaths were attributed to AEs. Cytokine release syndrome occurred in 4 of 8 patients (50%), but all patients recovered with treatment.¹

To be eligible for the study, patients needed to have histologically confirmed synovial sarcoma, a surgically unresectable tumor, progressing or recurrent synovial sarcoma that has been treated with 1-4 regimens of systemic chemotherapy including anthracycline, a tumor expressing NY-ESO-1, measurable lesions evaluable by RECIST v1.1, an ECOG performance status of 0-2, and no severe damage of the major organs. Patients were excluded from the study if they had any of the following conditions: unstable angina, cardiac infarction, heart failure, uncontrolled diabetes, uncontrolled hypertension, active infection, interstitial pneumonia or lung fibrosis, or active autoimmune disease that requires steroids or immunosuppressive therapy.²

“Additional confirmation, ideally with larger numbers of patients, is needed but this study…is expected to be a promising new strategy for the treatment of [synovial sarcoma],” study authors wrote.¹

REFERENCES

1. Kawai A, Ishihara M, Nakamura T, et al. Safety and efficacy of NY-ESO-1 antigen-specific T-cell receptor gene-transduced T lymphocytes in patients with synovial sarcoma: a phase I/II clinical trial. [published online ahead of print, 2023 Oct 4]. Clin Cancer Res. 2023;10.1158/1078-0432.CCR-23-1456. doi:10.1158/1078-0432.CCR-23-1456

2. Study of TBI-1301 (NY-ESO-1 T cell receptor gene transduced autologous T lymphocytes) in patients with synovial sarcoma. ClinicalTrials.gov. Updated June 2, 2022. Accessed October 12, 2023. https://clinicaltrials.gov/study/NCT03250325