Master Protocol to Assess Safety and Dose of First Time in Human Next Generation Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Advanced Solid Tumors

  • End date
    Feb 13, 2024
  • participants needed
  • sponsor
Updated on 7 October 2022
treatment regimen
primary cancer
targeted therapy


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


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 have shown objective responses. GSK3901961, GSK3845097 and GSK4427296 are next generation engineered T-cell receptor (TCR) T-cells, co-expressing the cluster of differentiation 8 (CD8) alpha cell surface receptor, targeting NY-ESO-1, co-expressing the dominant-negative TGF-beta receptor type II (dnTGF-beta RII) cell surface receptor, targeting NY-ESO-1, and engineered using the Epigenetically Reprogrammed (Epi-R) manufacturing process, respectively to potentially improve function. This is a master protocol evaluating first time in human T-cell therapies. It currently consists of three independent substudies, investigating GSK3901961, GSK3845097 and GSK4427296 in human leukocyte antigen (HLA)-A*02 positive participants with NYESO1+ previously treated advanced (metastatic or unresectable) synovial sarcoma (SS)/myxoid/round cell liposarcoma (MRCLS) and/or previously treated metastatic non-small cell lung cancer (NSCLC).

Condition Neoplasms
Treatment cyclophosphamide, Fludarabine, GSK3901961, GSK3845097, GSK4427296
Clinical Study IdentifierNCT04526509
Last Modified on7 October 2022


Yes No Not Sure

Inclusion Criteria

Participant must be >=18 years of age and weighs ≥40 kg on the day of signing informed consent
Participant must be positive for HLA-A _02:01, HLA-A_ 02:05, and/or HLA-A02:06 alleles
Participant's tumor must have tested positive for NY-ESO-1 and/or LAGE-1a expression by a GSK designated laboratory
Performance status: Eastern Cooperative Oncology Group of 0-1
Participant must have adequate organ function and blood cell counts 7 days prior to leukapheresis
Participant must have measurable disease according to RECIST v1.1
Additional criteria for participants with SS/ MRCLS
Participant has advanced (metastatic or unresectable) SS or MRCLS confirmed by local histopathology with evidence of disease-specific translocation
Participant has completed at least one standard of care (SOC) treatment including anthracycline containing regimen unless intolerant to or ineligible to receive the therapy. Participants who are not candidates to receive anthracycline should have received ifosfamide unless also intolerant to or ineligible to receive ifosfamide. Participants who received neoadjuvant/adjuvant anthracycline or ifosfamide based therapy and progressed will be eligible
Additional criteria for participants with non-small cell lung cancer (NSCLC)
Participant has Stage IV NSCLC as confirmed by histology or cytology
Prior therapies for participants lacking actionable genetic aberrations (i.e., wild type), per National Comprehensive Cancer Network (NCCN) guidelines: participant has been previously treated with or is intolerant to programmed death receptor-1 (PD)-1/Programmed death ligand 1 (PD-L1) checkpoint blockade therapy and has been previously treated with or is intolerant to a platinum-based chemotherapy. Adjuvant therapy will count as a regimen if completed within 6 months before relapse. Or for participants that harbors an actionable genetic aberration (e.g. BRAF, anaplastic lymphoma kinase [ALK]/ c-ros oncogene 1 [ROS1] etc.), per NCCN guidelines: participants has been previously treated with or is intolerant to SOC therapy, including targeted therapy, as recommended by NCCN or equivalent country-level guidelines (European Society for Medical Oncology [ESMO], National Institute for Health & Care Excellence [NICE]) . Or Investigator has decided that additional lines of SOC therapy after the first line are not in the participant's best interest

Exclusion Criteria

Any other prior malignancy that is not in complete remission
Central nervous system (CNS) metastases, with certain exceptions for CNS metastases in NSCLC as specified in the protocol
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 requiring steroids or other immunosuppressive treatments
Previous treatment with genetically engineered NY-ESO-1-specific T cells, NY-ESO-1 vaccine or NY-ESO-1 targeting antibody
Prior gene therapy using an integrating vector
Previous allogeneic hematopoietic stem cell transplant within the last 5 years or solid organ transplant
Washout periods for prior radiotherapy and systemic chemotherapy must be followed
Major surgery within 4 weeks prior to lymphodepletion
Pregnant or breastfeeding females
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