LYL132 / Lyell Immunopharma - 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

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

"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 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 and myxoid/round cell liposarcoma [Substudy 3, GSK4427296]. (ASCO 2022) - P1 | "Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy expressing an affinity-enhanced T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. Analyses will be descriptive. The master protocol is open for recruitment."

Clinical • IO biomarker • P2 data • Liposarcoma • Oncology • Sarcoma • Solid Organ Transplantation • Solid Tumor • Synovial Sarcoma • Transplantation • CTAG1B • CTAG2 • DDIT3 • EWSR1 • FUS • HLA-A

GSK axes Lyell cell therapy, passes programs to Adaptimmune (FierceBiotech) - "GSK has axed its NY-ESO-1 T-cell receptor (TCR) pact with Lyell Immunopharma, with the Big Pharma transferring the program to Adaptimmune. It means that months after stopping enrollment in a study of its first-generation NY-ESO-1 candidate, GSK has walked away from a $1 billion-plus pact with Lyell that could have delivered enhanced successors....Over the summer, Lyell warned the partnership faced 'new uncertainty' because GSK had stopped enrollment in a clinical trial of a first-generation NY-ESO-1 candidate after it delivered lackluster data....In a Securities and Exchange Commission filing, Lyell said its understanding is that the strategic review sparked by the lete-cel data led to GSK’s decision to terminate the partnered programs, LYL132 and LYL331. The winner from this decision appears to be Adaptimmune, which announced in a separate release today that it had gained possession of NY-ESO and another TCR T-cell program called PRAME."

Licensing / partnership • Oncology

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

Epigenetic Reprogramming (Epi-R™) Yields T-Cell Receptor Products with Improved Stemness, Metabolic Fitness, and Functional Activity in the Presence of Persistent Antigen Exposure (ASGCT 2022) - "Based on these promising pre-clinical data, LYL132 will be evaluated in the clinic to assess the impact of T-cell product persistence and stemness on anti-tumor efficacy and overall clinical outcomes. LYL132 is expected to begin a Phase 1 clinical trial in adult patients with advanced synovial sarcoma or myxoid/round cell liposarcoma in 2022."

Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B

Lyell Immunopharma to Present Preclinical Data for Two Product Candidates in Clinical Development at ASGCT Annual Meeting (GlobeNewswire) - "The presentations will highlight preclinical data characterizing two investigational products in Phase 1 clinical development...The first abstract presents preclinical data for LYL797 demonstrating that Gen-R and Epi-R can enhance and prolong anti-tumor functions of ROR1-targeting CAR T-cell therapy in solid tumor model systems. The second abstract presents preclinical data for LYL132 demonstrating that Epi-R creates populations of stemlike NY-ESO-1-targeting TCR T cells that lead to products with increased proliferative capacity and prolonged functional activity in the presence of persistent antigen exposure."

Preclinical • Oncology • Solid Tumor

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

Lyell Immunopharma Announces FDA Clearance of IND for LYL132, a T-Cell Receptor Therapy for Solid Tumors Being Developed in Collaboration with GSK (GlobeNewswire) - "Lyell Immunopharma...announced today that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application to initiate a Phase 1 clinical trial for LYL132, an investigational T-cell receptor (TCR) therapy for patients with solid tumors expressing New York esophageal squamous cell carcinoma 1 (NY-ESO-1) that the company is developing in collaboration with GSK....'We are eager to start multiple clinical trials that utilize our technologies to assess the potential benefits for patients with solid tumor cancers and also remain on track for two additional INDs by the end of this year'....The planned Phase 1 trial will assess LYL132 in patients with NY-ESO-1+ advanced synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS)."

IND • New P1 trial • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma