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 human engineered T-cell therapies, in participants with advanced tumours.

Trial Description

Primary Outcome:

• Substudy 1: Overall response rate (ORR)
• Substudy 2: Overall response rate (ORR) as assessed by central independent review

Secondary Outcome:

• Substudy 1 and 2: Time to response
• Substudy 1 and 2: Duration of response (DOR)
• Substudy 1 and 2: Disease control rate (DCR)
• Substudy 1 and 2: Progression free survival (PFS)
• Substudy 1 and 2: Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity
• Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL)
• Substudy 1 and 2: Number of participants with insertional oncogenesis (IO)
• Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters
• Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel
• Substudy 1 and 2: Time to Cmax (Tmax) of letetresgene autoleucel
• Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) of letetresgene autoleucel
• Substudy 2: Overall response rate (ORR) as determined by the local investigators
• Substudy 2: Overall Survival (OS)
• Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel

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. 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 (lete-cel) 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).

View this trial on ClinicalTrials.gov