First Patient in LION-1 Study Receives Immunotherapy Targeting Novel Molecule

The first patient in the Phase I clinical trial LION-1 has received treatment with a newly developed therapy. Over the course of the study, up to 46 patients will be treated with genetically modified immune cells (T cells) engineered to specifically target the ROR1 protein, which is expressed on the surface of various cancer cells. These specially equipped T cells are designed to recognize and attack tumor cells.

The trial is being conducted at the newly established Clinical Trial Center of the NCT WERA, affiliated with the Early Clinical Trial Unit (ECTU) led by Dr. Maria-Elisabeth Goebeler. The study team oversees the complex execution of the trial and coordinates the involved medical departments referring patients. The principal investigator of the LION-1 study is Prof. Dr. Hermann Einsele, Director of the Department of Internal Medicine II at University Hospital Würzburg (UKW) and spokesperson for NCT WERA.

The NCT is a long-term cooperation between the German Cancer Research Center (DKFZ), excellent partners in university medicine and other outstanding research partners at various locations in Germany.

World’s First CAR T Cell Study for Adrenocortical Carcinoma

Prior to treatment, the patient’s own T cells were harvested and genetically modified in the lab of the Fraunhofer Institute for Cell Therapy and Immunology (IZI) in Leipzig to express a chimeric antigen receptor (CAR). The treatment has now begun: the engineered immune cells were reinfused into the patient’s bloodstream, where the ROR1-CAR T cells are expected to identify and destroy cancer cells. The patient suffers from adrenocortical carcinoma, a rare and aggressive cancer, and had exhausted all standard treatment options.
“This is the world’s first CAR T cell study targeting this rare malignancy of the adrenal gland,” said treating endocrinologist Prof. Dr. Martin Fassnacht.

LION-1 Study Aims to Assess Safety of the Treatment

Prof. Dr. Sophia Danhof, a specialist in internal medicine and professor of Cellular Immunotherapy for Malignant Diseases, is overseeing the treatment and explains the study’s goals:
“We want to understand how the body tolerates the new therapy. What side effects may occur, and what is the appropriate dose? At the same time, we are hoping for early—albeit cautious—signs of efficacy. These could include tumor shrinkage, improvements in general health, or measurable immune responses.”

The study is investigating two patient cohorts: one with blood cancers such as mantle cell lymphoma or chronic lymphocytic leukemia, and the other with solid tumors including ovarian, breast, or adrenal cortex cancer. Up to 23 patients per group are expected to be enrolled.
“To reach these numbers, we are including additional study sites beyond Würzburg,” said Prof. Danhof. After enrolling the first ‘sentinel’ patients for dose escalation, the next recruitment phase will involve NCT sites in Berlin and Cologne. Patients from Erlangen, Regensburg, and Augsburg will be referred through the WERA alliance in Würzburg.

ROR1 Is a Promising Target for Hard-to-Treat Tumors

Establishing a therapy using ROR1-specific CAR T cells could be a breakthrough, especially for patients with solid tumors, who until now have had limited treatment options with immunotherapy.

Prof. Michael Hudecek, sponsor representative for the study, emphasized:
“ROR1 is a promising target because it is found on many cancer cells but rarely on healthy tissue.” His research team at the Chair of Cellular Immunotherapy at the University Hospital developed the ROR1-specific CAR T cells used in the trial.

A Trusted Partner for Personalized Manufacturing

Clinical-grade CAR T cell products for the LION-1 study are being manufactured at the Fraunhofer IZI in Leipzig under Good Manufacturing Practice (GMP) conditions. The institute brings extensive experience in producing CAR T cell therapies and also contributed to the preclinical development of the ROR1 therapy.

In the institute’s modern cleanrooms of the “GMP Cell and Gene Therapy” department, patient-specific immune cells are first isolated and enriched. The genetic information for the novel CAR receptor is then stably integrated into the T cell genome. The cells are subsequently expanded over several days.

Unlike currently approved CAR T cell therapies, this study uses the virus-free Sleeping Beauty transposon technology for gene transfer.

Following rigorous quality control and pharmaceutical release, the CAR T cell product is returned to the clinical site for patient treatment. Production of the CAR T cells for the second patient has already been completed, allowing treatment to begin shortly.

Text: Christina Bornschein / Chair of Cellular Immunotherapy