Overview

New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using adoptively transferred T-cells directed against NY-ESO-1/LAGE-1a have shown objective responses. Letetresgene autoleucel (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells. This protocol investigates Letetresgene autoleucel treatment in Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO1+ advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.

Principal investigator

Muhammad Furqan
Internal Medicine

Eligibility criteria

Inclusion Criteria:

  • Age >=18 years on the day of signing informed consent.
  • Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Participant is positive for any of the following alleles: human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05, and a) or HLA-A*02:06 by a validated test.
  • Participant's tumor meets the pre-defined threshold for expression of NY-ESO-1 and/or LAGE-1a.
  • Adequate organ function and blood cell counts, as defined in the protocol.
  • Predicted life expectancy that is >=24 weeks from leukapheresis.
  • Left ventricular ejection fraction >=45%.
  • Prior therapies prior to lymphodepletion: a) All participants with NSCLC lacking actionable genetic aberrations, per National Comprehensive Cancer Network (NCCN) guidelines (Arms A and B), need to have received at least one line of programmed death protein 1/programmed death protein 1 ligand (PD-1/PD-L1) checkpoint blockade therapy. For participants in the metastatic setting, PD-1/PD-L1 checkpoint blockade therapy must have been received either alone, in combination or sequentially with platinum-containing chemotherapy. OR b) All participants with NSCLC with actionable genetic aberrations, per NCCN guidelines (Arm C only), should have received appropriate targeted therapy following NCCN or equivalent country-level guidelines.
  • Disease progression at time of treatment, as defined in the protocol.
  • Measurable disease at time of treatment per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by local site investigator/radiology.

Exclusion Criteria:

  • Prior gene therapy using an integrating vector.
  • Prior allogeneic/autologous bone marrow or solid organ transplantation.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, dimethylsulfoxide (DMSO) or other agents used in the study
  • Severe hypersensitivity (>= Grade 3) to pembrolizumab and/or any of its excipients.
  • Active autoimmune disease that has required systemic treatment in past 2 years.
  • History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
  • Uncontrolled intercurrent illness.
  • Participant has active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein Barr virus (EBV), cytomegalovirus (CMV), syphilis, or human T lymphotropic virus (HTLV), as defined in protocol.
  • Known psychiatric or substance abuse disorders.
  • Symptomatic or untreated central nervous system (CNS) metastases.
  • Radiotherapy meeting any of the following criteria: a. >=50 Gray (Gy) to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the investigator's opinion would predispose patients to prolonged cytopenia after lymphodepletion. b. Radiotherapy to the target lesions within 3 months before lymphodepletion. A lesion with unequivocal progression may be considered a target lesion regardless of time from last radiotherapy dose.
  • Other protocol-defined inclusion/exclusion criteria may apply.
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Contact the study coordinator

Karen Parrott
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