Abstract A002: Autologous Tcells transduced with the affinity enhanced NY-ESO-1c259TCR in patients with synovial sarcoma expressing low levels of the NY-ESO-1 antigen

Background: NY-ESO-1c259 is an affinity optimized TCR recognizing an NY-ESO-1-derived peptide complexed with HLA-A*02 (SPEAR T-cells). NY-ESO-1c259TCR therapy induced responses in ~50% of patients whose tumors express high level NY-ESO-1 (NCT01343043). Here we report on preclinical studies of TCR activity and results from a cohort of patients whose tumors express low NY-ESO-1 levels. Methods: T-cell response against tumor-derived cell lines with differential NY-ESO-1 expression levels was assessed by ELISA. Patients had selected HLA subtypes (HLA-A*02:01, 02:05, 02:06) and advanced NY-ESO-1+ SS. In this cohort, tumors express NY-ESO-1 at ≥ 1+ in > 1% but 1×10e4 mRNA copies/10e6 reference gene transcripts. Ten patients in this cohort have been treated (as of 23Nov17). One died due to disease progression 2 days post infusion. Four have had a partial response (ORR 40%), and median duration of response was 8.5 weeks (range, 8-13). Antigen expression level by IHC (% 1+, 2+, and/or 3+), best overall response (BOR) by RECIST v1.1, and transduced cell expansion (copies/microgram DNA) are listed below for the 9 evaluable patients: Pt 264, 30% 1+/2+, PR, 86320; Pt 313, 90% 1+, PR, 45430; Pt 325, 10% 2+, PR, 13365; Pt 331, 40% 1+, 10% 2+, 10% 3+, PR, 197546; Pt 324, 50% 1+, 10% 2+, SD, 133334; Pt 305, 5% 1+, 5% 2+, 5% 3+, SD, 74855; Pt 322, 50% 1+, 10% 2+, SD, 54569; Pt 323, 20% 1+, 10% 2+, SD, 50912; Pt 211, 10% 1+, 20% 2+, 20% 3+, PD, 22627. Conclusions: In vitro assays can assess mRNA levels and protein expression of target antigen required for T-cell activation and cytotoxicity, predicting expression levels required for anti-tumor activity in vivo. The patient data suggest that affinity optimized TCRs can be used to treat tumors with low target antigen expression. Citation Format: Dejka Araujo, Sandra D9Angelo, George Demetri, Mihaela Druta, John Glod, Warren Chow, William Tap, Joana Senra, Rachel Abbott, Erin Van Winkle, Karen Chagin, Miguel Maroto, Elliot Norry, Malini Iyengar, Trupti Trivedi, Andrew Gerry, Rafael Amado, Crystal Mackall. Autologous Tcells transduced with the affinity enhanced NY-ESO-1c259TCR in patients with synovial sarcoma expressing low levels of the NY-ESO-1 antigen [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A002.