GSK3845097 / GSK - LARVOL DELTA

ZENYTH-ESO: Master Protocol to Assess 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 (clinicaltrials.gov) - P1 | N=12 | Terminated | Sponsor: 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.

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • CTAG1B • CTAG2 • HLA-A • PD-L1 • ROS1

Study of GSK3845097 in Previously Treated Participants With Advanced Synovial Sarcoma and Myxoid/Round Cell Liposarcoma (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: GlaxoSmithKline

Metastases • New P1 trial • Esophageal Squamous Cell Carcinoma • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • CTAG2 • HLA-A

SAFETY AND RECOMMENDED PHASE 2 DOSE OF NEXT GENERATION NY-ESO-1-SPECIFIC TCR T-CELLS IN HLA-A*02 PATIENTS WITH SYNOVIAL SARCOMA OR NON-SMALL CELL LUNG CANCER: MASTER PROTOCOL (SUBSTUDIES 1 AND 2) (CTOS 2021) - P1 | "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 • IO biomarker • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Organ Transplantation • Solid Tumor • Synovial Sarcoma • Transplantation • CD4 • CTAG1B • CTAG2 • HLA-A • TGFB1

ZENYTH-ESO: Master Protocol to Assess 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 (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting | N=67 ➔ 11 | Trial completion date: Feb 2024 ➔ Dec 2025 | Trial primary completion date: Feb 2024 ➔ Dec 2025

Combination therapy • Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • CTAG1B • CTAG2 • HLA-A • PD-L1 • ROS1

ZENYTH-ESO: Master protocol to assess the safety and recommended phase II dose of next generation NY-ESO-1-specific TCR T-cells in HLA-A*02 patients with synovial sarcoma, myxoid/round cell liposarcoma and non- small cell lung cancer [Substudy 1 (GSK3901961) and Substudy 2 (GSK3845097)] (DKK 2022) - P1 | "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."

Clinical • P2 data • Liposarcoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD8 • CTAG1B • CTAG2 • HLA-A • TGFB1

"Nice take - which I don't take ;) - but needs a small correction GSK3901961 is (was) CD8+ co-expression like ADAP SURPASS while GSK3845097 is (was) the dnTGF-beta RII modification and GSK4427296 is /was Epi-R" (@dhovekamp42)

CD8 • TGFB1

ZENYTH-ESO: Master Protocol to Assess 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 (clinicaltrials.gov) - P1 | N=67 | Recruiting | Sponsor: GlaxoSmithKline | N=50 ➔ 67

Combination therapy • Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • CTAG1B • CTAG2 • HLA-A • PD-L1 • ROS1

Master Protocol to Assess 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 (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: GlaxoSmithKline | N=38 ➔ 50

Combination therapy • Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • CTAG1B • CTAG2 • HLA-A • PD-L1 • ROS1

Engineering Cancer Antigen-Specific T Cells to Overcome the Immunosuppressive Effects of TGF-β. (PubMed, J Immunol) - "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."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Hematological Disorders • Hematological Malignancies • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Synovial Sarcoma • CTAG1B • HLA-A • IFNG • TGFB1

[VIRTUAL] Master protocol to assess the safety and recommended Phase 2 dose of next generation NY-ESO-1-specific TCR T-cells in HLA-A*02 patients with synovial sarcoma and non-small cell lung cancer (AACR 2021) - P1 | "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."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD4 • CTAG1B • CTAG2 • TGFB1

[VIRTUAL] Master protocol to assess safety and recommended phase 2 dose of next generation NY-ESO-1–specific TCR T-cells in HLA-A*02 patients with synovial sarcoma or non-small cell lung cancer (Substudies 1 and 2). (ASCO 2021) - P1 | "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."

Clinical • IO biomarker • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Organ Transplantation • Solid Tumor • Synovial Sarcoma • Transplantation • CD4 • CTAG1B • CTAG2 • TGFB1

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 (clinicaltrials.gov) - P1; N=38; Recruiting; Sponsor: GlaxoSmithKline; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTAG1B • PD-L1

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 (clinicaltrials.gov) - P1; N=38; Not yet recruiting; Sponsor: GlaxoSmithKline

Clinical • Combination therapy • New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • CTAG1B • PD-L1