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 Tumours

Official Title

Master Protocol to Assess the Safety and Recommended Phase 2 Dose of Next Generations of Autologous Enhanced NY-ESO-1/ LAGE-1a TCR Engineered T-cells, Alone or in Combination With Other Agents, in Participants With Advanced Tumours

Summary:

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

Trial Description

Primary Outcome:

• Substudy 1, 2 and 3: Frequency of dose limiting toxicities (DLTs)
• Substudy 1, 2 and 3:Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity

Secondary Outcome:

• Substudy 1, 2 and 3: Overall response rate (ORR)
• Substudy 1, 2 and 3: Duration of response (DOR)
• Substudy 1, 2 and 3: Maximum expansion/persistence (Cmax)
• Substudy 1, 2 and 3 : Time to Cmax (Tmax)
• Substudy 1, 2 and 3: Area under the concentration/persistence time curve from zero to time t (AUC[0-t])

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 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).

View this trial on ClinicalTrials.gov