LYL845 / Lyell Immunopharma - LARVOL DELTA

LYL845-101: A Study to Investigate LYL845 in Adults With Solid Tumors (clinicaltrials.gov) - P1 | N=39 | Terminated | Sponsor: Lyell Immunopharma, Inc. | N=108 ➔ 39 | Trial completion date: Sep 2027 ➔ Jan 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2025 ➔ Jan 2025; Pipeline Reprioritization

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • MSI

LYL845-101: A Study to Investigate LYL845 in Adults With Solid Tumors (clinicaltrials.gov) - P1 | N=108 | Active, not recruiting | Sponsor: Lyell Immunopharma, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Colorectal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • MSI

Lyell Pipeline Prioritization (GlobeNewswire) - "Lyell is discontinuing development of LYL797, its ROR1-targeted CAR T-cell product candidate to focus on the Phase 1 clinical trial of its next-generation ROR1-targeted CAR T-cell product candidate LYL119, which is expected to initiate enrollment of patients with platinum-resistant ovarian cancer or relapsed/refractory endometrial cancer this year or early next year. The LYL845 tumor-infiltrating lymphocyte (TIL) program is also being discontinued as the clinical data in patients with advanced melanoma did not meet our rigorous pre-determined criteria for continued development. Its next-generation TIL and rejuvenation programs that are in preclinical development will also be discontinued."

Discontinued • New trial • Endometrial Cancer • Melanoma • Ovarian Cancer • Solid Tumor

Lyell Immunopharma Reports Business Highlights and Financial Results for the Second Quarter 2024 (GlobeNewswire) - "Second Quarter Updates and Recent Business Highlights:...(i) LYL845:...Initial clinical and translational data from the Phase 1 trial of LYL845 in patients with advanced melanoma are expected in the second half of 2024; (ii) LYL119:...An IND application for LYL119 has received clearance from the U.S. Food and Drug Administration (FDA). The Phase 1 trial is designed as an open‑label dose‑escalation and ‑expansion trial in patients with ROR1‑positive solid tumors and will initially enroll patients with ROR1‑positive platinum‑resistant ovarian cancer or endometrial cancer....Initial clinical data are expected in the second half of 2025."

IND • New P1 trial • P1 data • Endometrial Cancer • Melanoma • Ovarian Cancer

Lyell Immunopharma Reports Business Highlights and Financial Results for the First Quarter 2024 (GlobeNewswire) - "LYL845: Enrollment in the Phase 1 clinical trial of LYL845 is ongoing. The study includes patients with relapsed or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer....Initial clinical and translational data from the Phase 1 trial of LYL845 are expected in the second half of 2024."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor

Lyell Immunopharma Reports Business Highlights and Financial Results for the Fourth Quarter and Full Year 2023 (GlobeNewswire) - "LYL845: Enrollment in the Phase 1 clinical trial for LYL845 is ongoing. The study includes patients with relapsed and/or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer. Initial clinical and translational data from the Phase 1 trial of LYL845 are expected in the second half of 2024....Epi-R P2 is expected to be incorporated into the Phase 1 trial of LYL845 in 2024."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study to Investigate LYL845 in Adults With Solid Tumors (clinicaltrials.gov) - P1 | N=108 | Recruiting | Sponsor: Lyell Immunopharma, Inc.

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • MSI

A Study to Investigate LYL845 in Adults With Solid Tumors (clinicaltrials.gov) - P1 | N=108 | Recruiting | Sponsor: Lyell Immunopharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • MSI

Lyell Immunopharma Receives FDA Orphan Drug Designation for LYL845 for the Treatment of Melanoma (GlobeNewswire) - "Lyell Immunopharma, Inc...announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to LYL845, an investigational tumor infiltrating lymphocyte (TIL) product candidate for the treatment of patients with stage IIB-IV melanoma....Initial data from Lyell’s ongoing Phase 1 clinical trial are expected in 2024."

Orphan drug • P1 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

Lyell Immunopharma Reports Business Highlights and Financial Results for the Third Quarter 2023 (GlobeNewswire) - "Enrollment in the Phase 1 clinical trial for LYL845 is ongoing. The study includes patients with relapsed and/or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer. Initial clinical data from the Phase 1 trial of LYL845 are expected in 2024. Preclinical data on the Epi-R P2 manufacturing process designed to shorten TIL manufacturing time without impacting cell number and phenotype were presented at SITC. Epi-R P2 is expected to be incorporated into the Phase 1 trial in 2024."

P1 data • Trial status • Colorectal Cancer • Melanoma • Non Small Cell Lung Cancer

Phase 1 trial of LYL845, an autologous tumor-infiltrating lymphocyte (TIL) therapy enhanced with epigenetic reprogramming, for the treatment of advanced solid tumors (SITC 2023) - P1 | "Part B (dose-expansion) will treat 15-30 pts in each disease cohort at the recommended phase 2 dose range (RP2DR), determined in Part A. After TIL tumor tissue collection surgery and successful LYL845 manufacturing, pts receive fludarabine and cyclophosphamide followed 2-5 days later by a single infusion of LYL845. Exploratory objectives include measurement of tumor mutational burden, clonal diversity of the TIL drug product, T cell clonal expansion and persistence in the periphery and the presence of TIL drug product derived T cell clones in the tumor post-infusion. The trial is open and currently enrolling."

IO biomarker • Metastases • P1 data • Tumor mutational burden • Tumor-infiltrating lymphocyte • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • IL2 • TMB

Lyell Immunopharma Presentations at SITC Highlight New Nonclinical Data on Product Candidates and Innovative Technology to Shorten TIL Manufacturing (GlobeNewswire) - "Two additional presentations highlight the design of Lyell’s two ongoing Phase 1 clinical trials in progress....A presentation titled 'Phase 1 trial of LYL797, a ROR1-targeted CAR T-cell therapy enhanced with genetic and epigenetic reprogramming, in advanced triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC)' describes the design of this dose-escalation, dose-expansion Phase 1 trial in patients with ROR1-positive relapsed refractory TNBC and NSCLC; A presentation titled 'Phase 1 trial of LYL845, an autologous tumor-infiltrating lymphocyte (TIL) therapy enhanced with epigenetic reprogramming, for the treatment of advanced solid tumors' describes the design of this dose-escalation, dose-expansion Phase 1 trial in advanced solid tumors, including advanced melanoma, NSCLC and colorectal cancer."

Clinical protocol • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Lyell Immunopharma Announces the Acceptance of Six Abstracts for Presentation at 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "Two additional presentations highlight the design of Lyell’s ongoing Phase 1 clinical trials in progress: LYL797, a ROR1-targeted CAR T-cell therapy being evaluated in a Phase 1 trial in patients with relapsed refractory triple-negative breast cancer and non-small cell lung cancer, and LYL845, a tumor infiltrating lymphocyte (TIL) therapy being evaluated in a Phase 1 trial in advanced solid tumors."

Clinical protocol • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Lyell Immunopharma Reports Business Highlights and Financial Results for the Second Quarter 2023 (GlobeNewswire) - "Enrollment in the Phase 1 clinical trial for LYL845 is ongoing. The study includes patients with relapsed and/or refractory metastatic or locally advanced melanoma, non-small cell lung cancer and colorectal cancer and is now open at nine sites. Initial clinical data from the Phase 1 trial of LYL845 are expected in 2024."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Thoracic Cancer

Lyell Immunopharma Reports Business Highlights and Financial Results for the Fourth Quarter and Full Year 2022 (GlobeNewswire) - "Enrollment in the Phase 1 clinical trial of LYL797 is ongoing. Initial clinical data from the Phase 1 trial of LYL797 are expected in the first half of 2024....An IND for LYL119 is expected to be submitted in the first half of 2024....Announced clearance of the IND for LYL845 in October 2022; enrollment in the Phase 1 clinical trial for LYL845 is ongoing. Initial clinical data from the Phase 1 trial of LYL845 are expected in 2024. "

IND • P1 data • Trial status • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Thoracic Cancer • Triple Negative Breast Cancer

Lyell Immunopharma to Participate in 41st Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Lyell Immunopharma, Inc...announced today that members of its senior management team will present and participate in the 41st Annual J.P. Morgan Healthcare Conference on Tuesday, January 10 at 4:30 pm Pacific Time. At the conference, Lyell executives will highlight the company’s growing pipeline of product candidates targeting solid tumors and T-cell reprogramming technologies, including its: Lead CAR T cell and TIL product candidates, LYL797 and LYL845, which are in Phase 1 clinical development; Second-generation ROR1 targeting CAR T-cell product candidate, LYL119, that incorporates two new reprogramming technologies; Newest stackable genetic and epigenetic reprogramming technologies: NR4A3 gene knockout, that is being incorporated along with c-Jun overexpression to enhance the functional activity of CAR T cells; and; Stim-RTM, a programmable cell-signaling platform that optimizes signaling parameters during T-cell activation in order to generate more potent CAR T cells."

Clinical data • Pipeline update • Oncology • Solid Tumor

The Epi-RTM technology produces a polyclonal TIL product (LYL845) with a greater expansion success rate across hot and cold tumors, improved product phenotype, and maintenance of TCR diversity (SITC 2022) - "Conclusions Results from research- and large-scale productions demonstrate that the Epi-R technology enables successful TIL expansion from both immunologically hot and cold tumors, while maintaining a greater proportion of stem-like T cells that demonstrate better metabolic fitness with preserved polyclonality (i.e., maintenance of tumor-reactive TCR diversity) across all 3 tumor types investigated. These findings support the clinical development of LYL845 in an upcoming first-in-human Phase 1 clinical trial."

Clinical • IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • CD4 • CD8

The Epi-RTM technology produces a polyclonal TIL product (LYL845) with diverse tumor-reactive clones that have stem-like qualities and anti-tumor function (SITC 2022) - "Conclusions Pre-clinical data show that LYL845 is an expanded TIL product that preserves tumor-reactive clones with stem-like qualities. Based on these promising preclinical data, we plan to evaluate LYL845 for safety, tolerability, and anti-tumor activity in an upcoming first-in-human Phase 1 clinical trial."

Melanoma • Oncology • Solid Tumor

Lyell Immunopharma Presents New Data at SITC Highlighting its Growing Pipeline of T – Cell Reprogramming Technologies and Product Candidates Targeting Solid Tumors (GlobeNewswire) - "Lyell Immunopharma...is presenting preclinical data at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) on its product candidates and new genetic and epigenetic reprogramming technologies....Two presentations on Friday, Nov. 11 highlight preclinical data on LYL845....The first presentation...showcases the ability of Epi-R technology to successfully expand TIL across three tumor types as compared to the standard (control) process....The second presentation...highlights bioinformatic analyses demonstrating that LYL845 products expanded using Epi-R technology were highly polyclonal and retained putative tumor reactive clones with increased stemness and reduced exhaustion-associated genes compared to TIL products derived from the standard process."

Preclinical • Oncology • Solid Tumor

A Study to Investigate LYL845 in Adults With Solid Tumors (clinicaltrials.gov) - P1 | N=108 | Not yet recruiting | Sponsor: Lyell Immunopharma, Inc.

New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • MSI

Lyell Immunopharma Announces FDA Clearance of its IND for LYL845, a TIL Product Candidate Enhanced with its Novel Epigenetic Reprogramming Technology for Solid Tumors (GlobeNewswire) - "Lyell Immunopharma...announced today that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to initiate a Phase 1 clinical trial for LYL845. LYL845 is an investigational tumor infiltrating lymphocyte (TIL) therapy enhanced with Lyell’s Epi-R™ technology for patients with relapsed and/or refractory metastatic or locally advanced melanoma and other select solid tumors....Patient screening for the Phase 1 trial is set to begin over the coming months, and initial clinical data is expected in 2024."

IND • New P1 trial • P1 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

Lyell Immunopharma to Present Preclinical Data Highlighting New T-Cell Reprogramming Technologies and its Growing Pipeline at 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "Lyell Immunopharma....announced today that five abstracts highlighting preclinical data on its product candidates and new genetic and epigenetic reprogramming technologies were accepted for presentation at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC)....The combination of these two genetic reprogramming technologies is being incorporated in Lyell’s new product candidate, LYL119, a second generation investigational ROR1 targeting CAR T-cell therapy....Two presentations will feature preclinical data from LYL845...designed to create products with higher proportions of stem-like T cells. Lyell will also present preclinical data from its new genetic reprogramming technology designed to further limit T cell exhaustion, as well as data on its new epigenetic reprogramming technology, Stim-R™, designed to generate a more potent T cell product by controlling delivery of activation molecules during T cell production."

Preclinical • Oncology

Lyell Immunopharma Reports Fourth Quarter and Full Year 2021 Financial Results and Business Highlights (GlobeNewswire) - "Full Year 2021, Recent Highlights, and Upcoming Milestones: (i) On track to submit an IND in the second half of 2022 for LYL845, a tumor infiltrating lymphocyte (TIL) therapy; (ii) GSK has communicated to Lyell that due to updated manufacturing timing, the IND for LYL331 is likely to be submitted in late 2022 / early 2023. LYL331 is a TCR therapy for patients with solid tumors expressing NY-ESO-1."

IND • Oncology • Solid Tumor