Skip to main content
Premium Trial:

Request an Annual Quote

Lyell Immunopharma Receives IND Clearance for Phase I Trial of CAR T-Cell Therapy for ROR1-Expressing TNBC, NSCLC

NEW YORK – Lyell Immunopharma said on Thursday that the US Food and Drug Administration has given it the go-ahead to begin a Phase I clinical trial to assess the activity of its investigational CAR T-cell therapy in ROR1-positive breast and lung cancer patients.

The FDA's clearance of Lyell's investigational new drug, or IND, application for LYL797 will allow the firm to begin screening previously treated triple-negative breast cancer patients for ROR1 expression for enrollment in the dose escalation portion of the Phase I trial in the first quarter of 2022. Once Lyell establishes the right dose of LYL797, the trial will expand to the dose expansion phase and include ROR1-positive non-small cell lung cancer patients. The South San Francisco, California-based company plans to enroll 15 patients with each cancer type.

The primary endpoints in the trial will be safety and tolerability, but Lyell will also assess LYL797's anti-tumor activity and pharmacokinetic profile as well as exploratory biomarkers of T-cell function, including exhaustion and stemness. Lyell expects to report initial data in 2023.

LYL797 is a CAR T-cell product that involves genetically reprogramming patients' immune cells to express ROR1-targeting CARs. By incorporating two additional technologies, Gen-R and Epi-R, into its product, Lyell has designed LYL797 to potentially overcome the barriers that have prevented CAR T-cell therapies from benefiting solid tumor patients. With Gen-R, the firm modifies the cells ex vivo to overexpress the protein c-Jun, which could make CAR T cells less susceptible to exhaustion by way of the AP-1 pathway. With the proprietary method Epi-R, moreover, the firm says it has created a product with "durable stemness," meaning the T cells can self-renew, proliferate, and persist once they're infused back into the patient.

According to a statement from Rick Klausner, chair of Lyell's board of directors, the FDA's clearance of Lyell's first IND also marks the first time that the agency has cleared an IND application that "includes a specific genetic modification to address T-cell exhaustion."

"We look forward to testing this first-generation technology platform in the clinic, thus specifically addressing the question of exhaustion as a barrier to successful cell therapy in solid tumors," Klausner said.

Last year, Lyell announced a partnership with Sarah Cannon, the Cancer Institute of HCA Healthcare, to develop and evaluate T-cell therapies.

Beyond LYL797, Lyell plans to submit three other INDs by the end of 2022, including applications for its autologous tumor infiltrating lymphocyte therapies as well as its partnered T-cell receptor therapies.