Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
Condition: Neoplasms
MeSH terms: Liposarcoma; Sarcoma, Synovial; Liposarcoma, Myxoid
Intervention: Letetresgene autoleucel; Cyclophosphamide; Fludarabine
Intervention description: Letetresgene autoleucel will be administered.; Cyclophosphamide will be used as a lymphodepleting chemotherapy.; Fludarabine will be used as a lymphodepleting chemotherapy.
Intervention MeSH terms: Cyclophosphamide; Fludarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 10 Years
Healthy volunteers: No
Keywords: Adoptive T-cell therapy; Letetresgene autoleucel; Lete-cel; GSK3377794

Summary:

      This trial will evaluate safety and efficacy of human engineered T-cell therapies, in
      participants with advanced tumors. This trial is a sub study of the Master study NCT03967223.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must be greater than or equal to 10 years of age on the day of signing
             informed consent.

          -  Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles
             by a designated central laboratory

          -  Participant's tumor is positive for NY-ESO-1 expression by a designated central
             laboratory.

          -  Participant has a diagnosis of synovial sarcoma (SS) or myxoid/round cell liposarcoma
             (MRCLS)

          -  Performance status: dependent on age - Lansky > 60, Karnofsky > 60, Eastern

          -  Cooperative Oncology Group 0-1.

          -  Participant must have adequate organ function and blood cell counts, within 7 days
             prior to leukapheresis.

          -  At time of treatment, participant has measurable disease according to RECIST v1.1.

          -  Consultation for prior history per protocol specifications.

        Exclusion Criteria:

          -  Central nervous system metastases.

          -  Any other prior malignancy that is not in complete remission.

          -  Clinically significant systemic illness.

          -  Prior or active demyelinating disease.

          -  History of chronic or recurrent (within the last year prior to leukapheresis) severe
             autoimmune or immune mediated disease (e.g. Crohn's disease, systemic lupus) requiring
             steroids or other immunosuppressive treatments.

          -  Previous treatment with genetically engineered NY-ESO-1-specific T cells.

          -  Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.

          -  Prior gene therapy using an integrating vector.

          -  Previous allogeneic hematopoietic stem cell transplant.

          -  Washout periods for prior radiotherapy and systemic chemotherapy must be followed.

          -  Participant had major surgery in less than or equal to 28 days of first dose of study
             intervention.

          -  Prior radiation exceeds protocol specified limits.