Phase 1 trial testing CAR T-cell therapy GC012F in SLE launches

Study is recruiting adults ages 18-70 with systemic lupus erythematosus

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Gracell Biotechnologies announced the launch of a Phase 1 clinical trial in China testing GC012F, its experimental dual FastCAR T-cell therapy, for hard-to-treat systemic lupus erythematosus (SLE).

The investigator-initiated trial (NCT05846347), underway at The First Affiliated Hospital of the Zhejiang University College of Medicine, is recruiting adults ages 18-70 with SLE. The study is expected to conclude in April 2025.

Enrolled participants will receive a single injection of different doses of GC012F and be monitored for side effects and toxicity. The study aims to determine what is the best dose of GC012F that should be used in future trials of SLE.

Meanwhile, the company is preparing the submission of an investigational new drug (IND) application requesting authorization to start testing GC012F in human trials in the U.S. and China.

“This study of GC012F in SLE marks an important next step in GC012F’s development as we look to confirm its potential in autoimmune diseases and prepare the IND submission in both U.S. and China,” William Cao, PhD, Gracell’s founder, chairman, and CEO, said in a company press release.

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CAR T-cell therapy uses patient’s immune T-cells

In SLE, the most common form of lupus, B-cells produce harmful self-reactive antibodies (autoantibodies) that target and attack the body’s own tissues.

Common therapeutic approaches include the use of  immunosuppressants, as well as medications that specifically target and destroy B-cells, such as rituximab. However, these approaches have shown limited efficacy, especially for people with more severe disease that become treatment-resistant (refractory). This is thought to be due to the fact that many B-cells and their descendants, called plasma cells, escape being eliminated by these approaches.

CAR T-cell therapy uses a patient’s immune T-cells, which are engineered in the lab to express a lab-made receptor, or chimeric antigen receptor (CAR), that’s specifically designed to recognize a disease-associated protein.

GC012F is an experimental CAR-T cell therapy originally designed to treat patients with multiple myeloma, a rare blood cancer. Modified T-cells in GC012F are engineered to simultaneously target two proteins: the B-cell maturation antigen (BCMA) and the CD19 protein, which are both present in B-cells and plasma cells.

SLE is a new area of interest for Gracell, following results from a small compassionate-use trial in which a CD19 CAR T-cell therapy was used to treat five SLE patients with refractory disease. Results showed the therapy led to sustained disease remission, and was highly specific, preventing the autoimmune reactions that drive SLE, but without impairing the general function of the immune system.

Gracell believes that by targeting both CD19 and BCMA, GC012F may lead to deeper and wider depletion of B-cells and plasma cells, when compared to CAR T-cell therapies targeting only CD19.

GC012F was created with Gracell’s proprietary FasTCAR platform, which can shorten the manufacturing process of CAR T-cell therapies to 22-36 hours from the standard of one to six weeks.

“Our lead candidate GC012F leverages several next-generation CAR-T technologies including CD19/BCMA dual-targeting and the FasTCAR next-day manufacturing. This cell therapy candidate has demonstrated strong efficacy and consistently favorable safety in the treatment of several hematological [blood-related] malignancies, and we look forward to extending this potentially curative treatment option to patients with autoimmune diseases, such as SLE,” Cao said.

In November 2021, the U.S. Food and Drug Administration granted orphan drug designation to GC012F for the treatment of multiple myeloma, in order to accelerate its clinical development and regulatory review.