Background: NY-ESO-1 is expressed in ~70% of synovial sarcomas (SS). NY-ESO-1^c259T cells recognizing an NY-ESO-1 derived peptide complexed with HLA-A*02 are being studied in SS. Methods: Eligible patients (pt) are HLA-A*02:01, 02:05 or 02:06, with unresectable, metastatic or recurrent SS expressing NY-ESO-1. Primary endpoint of ORR (CR+PR) is evaluated in high (≥ 50% tumor cells express 2+/3+) and low (≥ 1+ in ≥ 1% cells, not exceeding 2+/3+ in ≥ 50% cells) NY-ESO-1 expressers with different lymphodepleting regimens. Secondary endpoints are safety, DOR, PFS, OS, and gene-marked cell persistence. Lymphocytes are obtained by leukapheresis, isolated, activated, transduced to express NY-ESO-1^c259T, and expanded. Target dose is 1–6 × 10⁹cells. Disease is assessed at wk 4, 8 and 12 post-T-cell infusion, and then every 3 months. Results: 34 pt have been enrolled with 24 treated. 50% are male; median age is 30 yr (range 15 – 73). 12/15 pt in cohort 1 were treated. ORR was 50% (1 CR; 5 PR). Time to response was 6 wk (range 4-9) and median DOR 31 wk (range 13-72). Cohort 3 was closed due to only 1 PR out of 5 pt. Evaluation is ongoing in cohorts 2 (6 enrolled; 5 treated) and 4 (8 enrolled; 2 treated) as of 1/9/17. The most common AE are leukopenia (96%), nausea and pyrexia (88%), neutropenia (88%), lymphopenia (83%), anemia (79%), and thrombocytopenia (79%). 11 events of CRS were reported (3 G3; 1 G4), with no events of seizure, cerebral edema or fatal neurotoxicity; all resolved with supportive therapy. One fatal SAE (bone marrow failure) occurred in cohort 2; investigations have not identified a mechanism by which NY-ESO-1^c259T may have caused this event. Conclusions: NY-ESO-1^c259T has promising efficacy and acceptable safety. CRS is not associated with severe neurotoxicity and appears manageable with appropriate supportive care. Cohort 3 data indicate that Flu may be important for efficacy. Efficacy and safety data will be further evaluated and presented. Clinical trial information: NCT01343043

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