GSK3901961 / Adaptimmune - 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 GSK3901961 In Previously Treated Advanced (Metastatic OR Unresectable) Synovial Sarcoma/ Myxoid/Round Cell Liposarcoma, and Previously Treated Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=7 | Terminated | Sponsor: GlaxoSmithKline

Metastases • New P1 trial • Esophageal Squamous Cell Carcinoma • Liposarcoma • Lung Cancer • Non Small Cell Lung Cancer • 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 Substudy 1 (GSK3901961), Cohort 1: a first-in-human study 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 non-small cell lung cancer (DKK 2022) - P1 | "Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy expressing an affinity-enhanced T cell receptors (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. This study is recruiting. This substudy will evaluate the safety and efficacy of GSK3901961 in NSCLC."

Clinical • IO biomarker • P1 data • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CTAG1B • CTAG2 • HLA-A

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

[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

[VIRTUAL] CD8α-Enhanced NY-ESO-1-Specific TCR T Cells (GSK3901961) in HLA-A*02 Patients with NSCLC: Master Protocol Substudy 1 (IASLC-WCLC 2020) - P1 | "Introduction Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy engineered to express a modified T cell receptor (TCR) to improve recognition of NY-ESO-1 and/or LAGE-1a expressing cancer cells. The study is currently open and recruiting. Figure 1: Study design"

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD4 • CTAG1B • CTAG2 • EGFR • PD-L1 • ROS1

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

[VIRTUAL] CD8Α-ENHANCED NY-ESO-1-SPECIFIC TCR T CELLS (GSK3901961) IN HLA-A*02 PATIENTS WITH NSCLC: MASTER PROTOCOL SUBSTUDY 1 (EBMT 2021) - P1 | "Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy engineered to express a modified T cell receptor (TCR) to improve recognition of NY-ESO-1 and/or LAGE-1a expressing cancer cells. Exploratory endpoints include laboratory parameters, overall survival, progression-free survival, disease control rate, time to response, and anti-GSK3901961 titers. The study is currently open and recruiting."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD4 • CTAG1B • CTAG2 • PD-L1 • ROS1

[VIRTUAL] CD8Α-ENHANCED NY-ESO-1-SPECIFIC TCR T CELLS (GSK3901961) IN HLA-A*02 PATIENTS WITH NSCLC: MASTER PROTOCOL SUBSTUDY 1 (EBMT 2021) - P1 | "Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy engineered to express a modified T cell receptor (TCR) to improve recognition of NY-ESO-1 and/or LAGE-1a expressing cancer cells. Exploratory endpoints include laboratory parameters, overall survival, progression-free survival, disease control rate, time to response, and anti-GSK3901961 titers. The study is currently open and recruiting."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD4 • CTAG1B • CTAG2 • PD-L1 • ROS1

[VIRTUAL] CD8Α-ENHANCED NY-ESO-1-SPECIFIC TCR T CELLS (GSK3901961) IN HLA-A*02 PATIENTS WITH NSCLC: MASTER PROTOCOL SUBSTUDY 1 (EBMT 2021) - P1 | "Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy engineered to express a modified T cell receptor (TCR) to improve recognition of NY-ESO-1 and/or LAGE-1a expressing cancer cells. Exploratory endpoints include laboratory parameters, overall survival, progression-free survival, disease control rate, time to response, and anti-GSK3901961 titers. The study is currently open and recruiting."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD4 • CTAG1B • CTAG2 • PD-L1 • ROS1

[VIRTUAL] CD8Α-ENHANCED NY-ESO-1-SPECIFIC TCR T CELLS (GSK3901961) IN HLA-A*02 PATIENTS WITH NSCLC: MASTER PROTOCOL SUBSTUDY 1 (EBMT 2021) - P1 | "Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy engineered to express a modified T cell receptor (TCR) to improve recognition of NY-ESO-1 and/or LAGE-1a expressing cancer cells. Exploratory endpoints include laboratory parameters, overall survival, progression-free survival, disease control rate, time to response, and anti-GSK3901961 titers. The study is currently open and recruiting."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD4 • CTAG1B • CTAG2 • PD-L1 • ROS1