Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and / or LAGE-1a Positive Solid Tumors

This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors.

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.

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 (lete-cel, GSK3377794) is the first generation of NY-ESO-1 specific T-cell

receptor engineered T cells. This is a master protocol investigating T-cell therapies. It

will initially consist of a core protocol with two independent substudies investigating

Letetresgene autoleucel in previously untreated (1L) Human Leukocyte Antigen (HLA)-A*02+

participants with NY-ESO-1+ advanced (metastatic or unresectable) synovial sarcoma (SS) or

myxoid/round cell liposarcoma (MRCLS) (Substudy 1) and Letetresgene autoleucel as second line

or higher (2L+) treatment in HLA-A*02+ participants with NY-ESO-1+ advanced (metastatic or

unresectable) SS or MRCLS who have progressed following treatment with anthracycline based

chemotherapy (Substudy 2).

Trial Phase Phase II

Trial Type Treatment

Lead Organization
GlaxoSmithKline

• Primary ID 208467
• Secondary IDs NCI-2019-05288
• Clinicaltrials.gov ID NCT03967223