letetresgene autoleucel engineered t cells in ny-eso-1 positive participants with advanced myxoid/ round cell liposarcoma

Conditions: Neoplasms

Summary: this trial will evaluate safety and efficacy of letetresgene autoleucel (gsk3377794) in participants with advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.

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.

Eligibility criteria:
inclusion criteria: * participant is greater than equal to (\>=)18 years of age at the time of signing the study informed consent. * participant has a diagnosis of advanced (metastatic or inoperable) high grade myxoid liposarcoma / myxoid round cell liposarcoma confirmed histologically and by the presence of the reciprocal chromosomal translocation t(12;16) (q13;p11) or t(12; 22) (q13;q12). * participant has measurable disease according to recist v1.1 criteria. * participant must have previously received or be intolerant to anthracycline based therapy for advanced (metastatic or inoperable) disease. * participants who received neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of completion of therapy will be eligible. * participant must be hla a\*02:01, hla a\*02:05 and/or hla-a\*02:06 positive. * participant's tumor (either the most recent archival specimen or a fresh biopsy) is positive for ny-eso-1 expression by a designated central laboratory. * participant has an eastern cooperative oncology group (ecog) performance status 0-1. * participant has a left ventricular ejection fraction \>=45%. * participant is fit for apheresis and has adequate venous access for the cell collection. * participants must satisfy pregnancy and contraceptive requirements per protocol and have adequate organ function per protocol specified values. exclusion criteria: * any previous gene therapy using an integrating vector. * any previous allogeneic hematopoietic stem cell transplant. * participant has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study. * participant has history of chronic or recurrent (within the last year prior to screening) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments. * participant has known active brain or leptomeningeal metastases. * participant has other prior malignancy that is not in complete remission. * participant has uncontrolled intercurrent illness including, but not limited to: * (i) ongoing or active infection. * (ii) clinically significant cardiac disease * (iii) interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded, however, participants must not be oxygen dependent). * participant has active infection with human immunodeficiency virus (hiv), hepatitis b virus (hbv), ), hepatitis c virus (hcv) or human t-lymphotropic virus (htlv).

Keywords: myxoid/ round cell liposarcoma letetresgene autoleucel immuno-oncology t cell receptor leukapheresis ny-eso-1 adoptive tcr t-cell therapy