LION-1 Launches as First NCT WERA Bridging Study

Würzburg, Germany – Developing innovative immunotherapies is one of the key goals of NCT WERA, which has been a site of the National Center for Tumor Diseases (NCT) since 2023. The NCT is a long-term partnership between the German Cancer Research Center (DKFZ), outstanding university hospitals, and other leading research institutions at several locations across Germany.

Now, NCT WERA has reached a significant milestone. The LION-1 study has officially launched at University Hospital Würzburg (UKW). This Phase I NCT bridging study investigates the safety and tolerability of autologous ROR1-CAR T cells in patients with ROR1-positive tumors.

ROR1 as a Target in Hematologic and Solid Tumors

ROR1 is a surface protein found on cancer cells in both hematologic malignancies and solid tumors. In CAR T cell therapy, a patient's T cells are collected, genetically modified in the lab to express a specific receptor—called a chimeric antigen receptor (CAR)—and then reinfused into the patient. In blood cancers like leukemia and lymphoma, CD19 has proven to be an effective target, while BCMA is used for multiple myeloma. ROR1, on the other hand, is considered a cross-entity target, meaning one cell therapy product could potentially treat multiple tumor types.

LION-1 therefore includes two patient cohorts: one with mantle cell lymphoma and chronic lymphocytic leukemia, and another with ovarian cancer, triple-negative breast cancer, and adrenocortical carcinoma.

The study is led by Prof. Dr. Hermann Einsele, Director of the Department of Medicine II at UKW and spokesperson for NCT WERA. The project lead is Prof. Dr. Michael Hudecek, Chair of Cellular Immunotherapy at UKW, and the principal investigator is Prof. Dr. Sophia Danhof, who heads cellular immunotherapy at the newly established NCT Clinical Trial Center.

Research and Production in Würzburg

Preclinical work was also carried out in Würzburg. Prof. Hudecek and his research team successfully engineered a ROR1-specific CAR and demonstrated its anti-tumor efficacy in vitro and in vivo in hematologic models. The team also tested ROR1-CAR T cells in solid tumor models, including a cutting-edge microphysiological 3D tumor-on-chip system.

These ROR1-CAR T cells are manufactured using a modern, virus-free gene transfer method—unlike other CAR T therapies that still rely on viral vectors. This marks the first time that ROR1-directed CAR T cells will be tested clinically in humans.

Recruitment Begins at the NCT Clinical Trial Center in Würzburg

Following project initiation and team training, Prof. Einsele officially delegated the trial implementation to the study team on April 8, signing off as the site’s Principal Investigator (PI). The next day, recruitment began with the first patient consultation in the endocrinology department. A patient with adrenocortical carcinoma is now eligible to become the world’s first recipient of ROR1-CAR T cells. After the initial “sentinel” patients for dose escalation, NCT sites in Berlin and Cologne will begin recruitment. Sites in Erlangen, Regensburg, and Augsburg will refer their patients through the WERA alliance.