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

Official Title

Master Protocol to Assess the Safety and Antitumour Activity of Genetically Engineered NY-ESO-1-Specific (c259) T Cells, Alone or in Combination With Other Agents, in HLA-A2+ Participants With NY-ESO-1 and/or LAGE-1a Positive Solid Tumours (IGNYTE-ESO)

Summary:

This trial will evaluate safety and efficacy of GSK3377794 in patients with solid tumours, initially in patients with synovial sarcoma.

Trial Description

Primary Outcome:

• Substudy 1: Overall response rate
• Substudy 2: Overall response rate

Secondary Outcome:

• Substudy 1: Time to response
• Substudy 1: Duration of response
• Substudy 1: Disease control rate
• Substudy 1: Progression free survival
• Substudy 1: Number of patients with adverse events (AEs) and serious adverse events (SAEs)
• Substudy 1: Severity and duration of adverse events of special interest (AESIs)
• Substudy 1: Number of patients with replication competent lentivirus (RCL)
• Substudy 1: Number of patients with insertional oncogenesis
• Substudy 1: Change from Baseline in hematology parameters: platelets
• Substudy 1: Change from Baseline in hematology parameters: hematocrit
• Substudy 1: Change from Baseline in hematology parameters: hemoglobin
• Substudy 1: Change from Baseline in hematology parameters: Red blood cell (RBC) count
• Substudy 1: Change from Baseline in hematology parameters: White blood cell (WBC) count
• Substudy 1: Change from Baseline in clinical chemistry parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
• Substudy 1: Change from Baseline in clinical chemistry parameters: Blood Urea Nitrogen (BUN)
• Substudy 1: Change from Baseline in clinical chemistry parameters: Total and Direct bilirubin, Creatinine
• Substudy 1: Change from Baseline in urine parameters: potential of hydrogen (pH)
• Substudy 1: Change from Baseline in urine parameters: glucose, protein, blood, bilirubin
• Substudy 1: T Cell Persistence of GSK3377794
• Substudy 2: Time to response
• Substudy 2: Duration of response
• Substudy 2: Disease control rate
• Substudy 2: Progression free survival
• Substudy 2: Overall survival
• Substudy 2: Number of patients with AEs and SAEs
• Substudy 2: Severity and duration of adverse events of special interest (AESIs)
• Substudy 2: Number of patients with RCL
• Substudy 2: Number of patients with insertional oncogenesis
• Substudy 2: Number of patients with positive anti-drug antibodies (ADA) against GSK3377794
• Substudy 2: Titers of ADA against GSK3377794
• Substudy 2: Change from Baseline in hematology parameters: platelets
• Substudy 2: Change from Baseline in hematology parameters: hematocrit
• Substudy 2: Change from Baseline in hematology parameters: hemoglobin
• Substudy 2: Change from Baseline in hematology parameters: Red blood cell (RBC) count
• Substudy 2: Change from Baseline in hematology parameters: White blood cell (WBC) count
• Substudy 2: Change from Baseline in clinical chemistry parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
• Substudy 2: Change from Baseline in clinical chemistry parameters: Blood Urea Nitrogen (BUN)
• Substudy 2: Change from Baseline in clinical chemistry parameters: Total and Direct bilirubin, Creatinine
• Substudy 2: Change from Baseline in urine parameters: potential of hydrogen (pH)
• Substudy 2: Change from Baseline in urine parameters: glucose, protein, blood, bilirubin
• Substudy 2: T Cell Persistence of GSK3377794

Adoptive T-cell therapy (ACT) is a therapeutic approach that uses T lymphocytes of patients with cancer, obtained by leukapheresis, with the aim of generating an anti-tumour T-cell immune response. New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumour-associated proteins that have been found in several tumour types. Clinical trials using adoptively transferred T-cells directed against NY-ESO-1/LAGE-1a have shown objective responses. GSK3377794 is the first generation of NY-ESO-1 specific T-cell receptor engineered T-cells. This is a master protocol that will initially consist of two substudies, investigating GSK3377794 in previously untreated patients with advanced metastatic synovial sarcoma (Substudy 1) and in patients with advanced metastatic synovial sarcoma who have progressed following treatment with anthracycline-based chemotherapy (Substudy 2).

View this trial on ClinicalTrials.gov