Master Protocol to Assess the 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

• Status: Recruiting
• Trial end date: 2024-02-12
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Cyclophosphamide; Fludarabine

Criteria

Eligibility Criteria:

Inclusion criteria:

• Participant must be >=18 years of age on the day of signing informed consent.

• Participant must be positive for Human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles.

• Participant's tumor is positive for NY-ESO-1 expression by a designated central 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 synovial sarcoma:

• Participant has advanced (metastatic or unresectable) synovial sarcoma confirmed by histology.

• Participant has received/completed treatment with anthracycline or with ifosfamide if intolerant to anthracycline for advanced (metastatic or unresectable) disease and progressed.

Additional criteria for participants with non-small cell lung cancer (NSCLC):

• Participant has Stage IV NSCLC as confirmed by histology or cytology.

• 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 a platinum-based chemotherapy. For NSCLC that harbors an actionable genetic aberration (e.g. BRAF, anaplastic lymphoma kinase [ALK]/ c-ros oncogene 1 [ROS1], etc ) per National Comprehensive Cancer Network (NCCN) guidelines, participant has also been previously treated with or is intolerant to the standard of care targeted therapy as recommended by NCCN or equivalent country-level guidelines (e.g. European Society for Medical Oncology [ESMO], National Institute for Health & Care Excellence [NICE], etc.).

Exclusion criteria:

• Central nervous system metastases, except in rare cases of NSCLC as specified in the protocol.

• 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 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.

• Major surgery <=28 days of first dose of study intervention.

• Pregnant or breastfeeding.