GSK3845097

P1, N=12, Terminated, GlaxoSmithKline | Trial completion date: Dec 2025 --> Jun 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Jun 2023; The study was terminated due to a change in GSK's R&D priorities.

P1, N=5, Terminated, GlaxoSmithKline

P1, N=11, Active, not recruiting, GlaxoSmithKline | Recruiting --> Active, not recruiting | N=67 --> 11 | Trial completion date: Feb 2024 --> Dec 2025 | Trial primary completion date: Feb 2024 --> Dec 2025

Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy expressing an affinity-enhanced T-cell recep- tor (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. This master protocol will evaluate the safety and efficacy of next generation NY-ESO-1 specific TCR-T cells in SS/MRCLS or NSCLC.

P1, N=67, Recruiting, GlaxoSmithKline | N=50 --> 67

P1, N=50, Recruiting, GlaxoSmithKline | N=38 --> 50

We previously generated specific peptide enhanced affinity receptor TCRs recognizing the HLA-A*02-restricted peptides New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/l-Ag family member-1A (TCR: GSK3377794, formerly NY-ESO-1) and melanoma Ag gene A10 (TCR: ADP-A2M10, formerly melanoma Ag gene A10). In this article, we show that exogenous TGF-β inhibited in vitro proliferation and effector functions of human T cells expressing these first-generation high-affinity TCRs, whereas inhibition was reduced or abolished in the case of second-generation TCRs coexpressed with dnTGFβRII (e.g., GSK3845097)...As an example, immunohistochemistry/RNAscope identified TGF-β-positive cells close to T cells in tumor nests and stroma, which had low frequencies of cells expressing IFN-γ in a non-small cell lung cancer setting. Coexpression of dnTGFβRII may therefore improve the efficacy of TCR-transduced T cells.

Objective: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy using a genetically modified T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1/LAGE-1a...Exploratory endpoints include laboratory parameters, overall survival, and anti-GSK3901961 or -GSK3845097 titers as applicable... This study was funded by GSK (209012; NCT04526509). Editorial support was provided by Eithne Maguire, PhD and Katie Crossland, PhD of Fishawack Indicia, part of Fishawack Health, UK; funded by GSK. This abstract was previously presented at the American Association for Cancer Research (April 10–15 and May 17–21, 2021) and the American Society of Clinical Oncology Annual Meeting (June 4–8, 2021).

Clinical Trial Registry Number: NCT04526509 Funding: GlaxoSmithKline (209012) Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy using a genetically modified T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1/LAGE-1a . Exploratory endpoints include laboratory parameters, overall survival, and anti-GSK3901961 or -GSK3845097 titers as applicable . Analyses will be descriptive.

Funding: GSK (209012; NCT04526509) Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy expressing a genetically modified T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. Exploratory endpoints include laboratory parameters, overall survival, and anti-GSK3901961 and anti-GSK3845097 titers for the respective substudies. The substudies are open and recruiting.

P1, N=38, Recruiting, GlaxoSmithKline | Not yet recruiting --> Recruiting