Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma
Sandra P. D’Angelo, Mihaela Druta, Brian A. Van Tine, David A. Liebner, Scott M. Schuetze, William D. Tap, Jessica Preston, Sophia Goodison, Jimson W. D’Souza, Gurpreet S. Kapoor, Sunil Suchindran, Stefan Zajic, Aishwarya Bhaskar, Heather Kaczynski, Jaegil Kim, Erika Klohe, Ellie Corigliano, Ioanna Eleftheriadou, Michael J. Nathenson, Neeta Somaiah
Abstract
PURPOSE: The cancer/testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target in myxoid/round cell liposarcoma (MRCLS). METHODS: T letetresgene autoleucel (lete-cel) in patients with human leukocyte antigen (HLA)-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-positive advanced/metastatic NY-ESO-1-expressing MRCLS. Patients underwent a reduced-dose (cohort 1) or standard-dose (cohort 2) lymphodepletion regimen (LDR). The primary end point was investigator-assessed overall response rate (ORR). Safety was assessed through adverse event (AE) reports. Correlative biomarker analyses were performed post hoc. The trial is registered at ClinicalTrials.gov (identifier: NCT02992743). RESULTS: Of 23 enrolled patients, 10 in cohort 1 and 10 in cohort 2 received lete-cel. Investigator-assessed ORR was 20% (95% CI, 2.5 to 55.6) and 40% (95% CI, 12.2 to 73.8), median duration of response was 5.3 months (95% CI, 1.9 to 8.7) and 7.5 months (95% CI, 6.0 to not estimable [NE]), and median progression-free survival was 5.4 months (95% CI, 2.0 to 11.5) and 8.7 months (95% CI, 0.9 to NE) in cohorts 1 and 2, respectively. AEs included cytokine release syndrome and cytopenias, consistent with T-cell therapy/LDR. Post hoc correlative biomarkers showed T-cell expansion and persistence in both cohorts. CONCLUSION: To our knowledge, this study is the first demonstrating the clinical promise of lete-cel in HLA-/NY-ESO-1-positive patients with advanced MRCLS.