2017 ASCO Annual Meeting!
Session: Developmental Therapeutics—Immunotherapy
Type: Oral Abstract Session
Time: Monday June 5, 1:15 PM to 4:15 PM
Location: Hall D1
Open label, non-randomized, multi-cohort pilot study of genetically engineered NY-ESO-1 specific NY-ESO-1c259t in HLA-A2+ patients with synovial sarcoma (NCT01343043).
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 3000)
Author(s): Crystal Mackall, William D. Tap, John Glod, Mihaela Druta, Warren Allen Chow, Dejka M. Araujo, Stephan A. Grupp, Brian Andrew Van Tine, Karen Chagin, Erin Van Winkle, Gabor Kari, Trupti Trivedi, Elliot Norry, Tom Holdich, Arundathy N. Bartlett-Pandite, Rafael G. Amado, Sandra P. D'Angelo; Stanford University School of Medicine, Stanford, CA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Moffitt Cancer Center, Tampa, FL; City of Hope, Duarte, CA; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Pediatric Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA; Washington University in St. Louis, St. Louis, MO; Adaptimmune Therapeutics PLC, Philadelphia, PA; Adaptimmune Therapeutics PLC, Abingdon, United Kingdom
Background: NY-ESO-1 is expressed in ~70% of synovial sarcomas (SS). NY-ESO-1c259T 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-1c259T, 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-1c259T may have caused this event. Conclusions: NY-ESO-1c259T 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
|1*||high||Fludarabine (Flu) 30 mg/m2/day × 4|
|2||low||cyclophosphamide (Cy) 1800 mg/m2/day × 2|
|3*||high||Cy 1800 mg/m2/day × 2|
|4||high||Flu 30 mg/m2/day × 3, Cy 600 mg/m2/day ×3|