Lyell Immunopharma Announces Initial Data from Phase 1 Trials Of LYL797

Lyell Immunopharma announces initial data from phase 1 trials of an ROR1-targeted CAR T cell product candidate, LYL797

Overview

Lyell Immunopharma, Inc, a clinical-stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumours or haematologic malignancies, reported the initial data from its phase 1 trial of LYL797 demonstrating dose-dependent clinical activity and that LYL797 CAR T cells expanded, infiltrated solid tumours and killed cancer cells in patients.

From the CEO: Lyell

• Based on these promising initial data,”We have expanded the cancer indications under evaluation in this trial to include patients with ovarian and endometrial cancers, and we plan to file an IND to initiate a new trial evaluating LYL797 in multiple myeloma and chronic lymphocytic leukaemia,” said Lynn Seely, M.D., Lyell’s president and CEO. 
• In addition, our IND for LYL119, a next generation ROR1-targeted CAR T-cell product candidate designed with four technologies to generate T cells with even greater capacity to resist exhaustion, has been cleared by the FDA, and we expect to report initial clinical data from the phase 1 trial in the second half of 2025.
• We remain on track to report initial clinical data from our lead TIL programme in the second half of this year. Our strong cash position enables us to advance multiple product candidates through critical clinical milestones and fund operations into 2027.

Advancement of Products 

• Lyell is advancing four wholly-owned product candidates. Two product candidates, LYL797 and LYL845, are in phase 1 clinical development, and LYL119 is entering phase 1 clinical development. 
• A second-generation tumor infiltrating lymphocyte (TIL) product candidate is in preclinical development.

LYL797

LYL797 – A ROR1-targeted CAR T-cell product candidate enhanced with anti-exhaustion technology designed for improved tumour infiltration and tumor cell killing

Phase 1 Clinical Trial

• Enrollment in the phase 1 clinical trial of LYL797 is ongoing. 
• The study was initiated in patients with relapsed/refractory triple-negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC). 
• Based on the initial clinical data that demonstrated dose-dependent anti-tumour activity, the trial has been expanded to include patients with platinum-resistant ovarian or endometrial cancers and an investigational new drug (IND) application is expected to be submitted in the second half of this year to initiate a second phase 1 clinical trial of LYL797 in multiple myeloma and chronic lymphocytic leukaemia (CLL).

Initial Tral Data in June 2024

• Initial clinical and translational data from the phase 1 clinical trial of LYL797 were reported in June 2024. 
• The initial dataset of 20 patients (16 patients with TNBC and four patients with NSCLC) demonstrated dose-dependent antitumor clinical activity and the ability of LYL797 CAR T cells to proliferate, infiltrate tumors and kill cancer cells in patients with relapsed/refractory disease. 
• Patients with TNBC treated with LYL797 had an objective response rate (ORR) of 40% and a clinical benefit rate (CBR) of 60% at the 150 x 106 CAR T cell dose level, with a CBR of 38% across all dose levels evaluable at the time data were reported. 

Adverse events- Common treatment-related adverse events (TRAE) in patients without lung metastases included Grade 1 and 2 cytokine release syndrome (CRS) and headache, and the expected cytopenia from lymphodepletion. 

• There were no reports of immune effector cell-associated neurotoxicity syndrome (ICANS) attributed to LYL797. 
• Pneumonitis occurred in some patients with lung metastases, including the index patient who experienced Grade 5 respiratory failure on Day 41. 
• All patients are now given dexamethasone prophylaxis and dose escalation is continuing separately and more gradually in patients with lung involvement. 
• No dose-limiting toxicities have been reported in patients without lung involvement.

Latest data - Updated data from the ongoing phase 1 trial in solid tumour indications, including the initiation of dose expansion, are expected in late 2024 – early 2025.

About LYL845 & Trial 

• LYL845 – A TIL product candidate epigenetically reprogrammed using Lyell’s proprietary Epi-R manufacturing protocol, designed for differentiated potency and durability.
• Enrollment in the phase 1 clinical trial of LYL845 is ongoing. The trial is designed to include patients with relapsed or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer.

Phase 1 Trial of LYL845 in 2024

• 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.
• LYL119 – A next-generation ROR1-targeted CAR T-cell product candidate incorporating four stackable and complementary anti-exhaustion technologies designed for enhanced potency.

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