China clears Phase 1/2 trial of GC012F in difficult-to-treat SLE

The experimental CAR T-cell therapy targets the proteins CD19 and BCMA

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by Margarida Maia |

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China’s regulatory body has given Gracell Biotechnologies the green light to launch a Phase 1/2 clinical trial testing GC012F, an experimental dual-targeting CAR T-cell therapy, in people with difficult-to-treat systemic lupus erythematosus (SLE).

The decision by China’s National Medical Products Administration comes shortly after the U.S. Food and Drug Administration cleared an investigational new drug application for another Phase 1/2 trial, expected to start this year.

“This milestone marks our rapid progress in advancing development of GC012F in rSLE [refractory, or treatment-resistant, SLE], an autoimmune disease with high unmet need,” William Cao, PhD, Gracell’s founder, chairman, and CEO, said in a press release.

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In SLE, autoimmune attacks are caused by self-reactive antibodies produced by immune B-cells against the body’s own tissues. The goal of treatment is to keep the immune system in check, but some people fail to respond to immunosuppressants or other medications.

GC012F is a form of CAR T-cell therapy specifically engineered to eliminate B-cells. The process involves retrieving T-cells, a different type of immune cell, from the patient and altering them to bear a synthetic surface protein known as a chimeric antigen receptor (CAR). This CAR guides the modified cells toward a predefined target CD19 and BCMA, two proteins on the surface of B-cells, which depletes B-cells and eases the symptoms of SLE.

“We’re relentlessly pursing clinical development of an innovative CD19/BCMA dual-targeting approach, which seeks to offer differentiated efficacy over other investigational therapies that only target CD19,” Cao said.

GC012F is being tested for difficult-to-treat SLE in an open-label, investigator-initiated Phase 1 clinical trial (NCT05846347) that is underway at a single site in Zhejiang University in Hangzhou, China. It is expected to conclude in 2025.

Early data presented at the annual ASH meeting

Early data from 12 adult patients who failed to respond to treatment with a range of medications were detailed in an abstract presented at the 65th American Society of Hematology Annual Meeting & Exposition, held in December in San Diego, California.

As part of the clinical trial, three patients received a single infusion of GC012F at a dose of one million cells per kilogram (kg) of body weight. Nine patients received a higher dose of two million cells/kg.

Over a median follow-up of 118.5 days (nearly four months), mean SLE Disease Activity Index-2000 (SLEDAI-2K) scores dropped from 18.3 to 1.5 points, indicating less-severe disease. All patients achieved a state of low disease activity.

Patients “were able to successfully discontinue all SLE-related medications, including glucocorticoids,” the researchers wrote. Moreover, “to date, no SLE flares have occurred,” they added.

All patients experienced low-grade cytokine release syndrome, a sudden, heightened inflammatory response that manifested as a fever. Eleven (91.7%) patients had life-threatening blood toxicity and one (8.3%) had severe blood toxicity. Within six months of CAR T-cell therapy, four (33.3%) patients developed an infection, which was treated.

The number of B-cells in circulation returned to normal about three months after treatment with GC012T. “These data suggest that CD19/BCMA CAR T-cell therapy is well tolerated and can induce rapid and durable remission in severe refractory SLE,” the researchers wrote.

GC012T also is being tested in rare cancer

GC012T also is being tested in multiple myeloma, a rare cancer that forms when B-cells grow uncontrollably, and other blood-borne cancers. Data from adults with multiple myeloma have shown that GC012F provides deep and durable responses, without being toxic to nerve cells.

“Combined with GC012F’s consistently favorable safety profile, based on the data from 60 patients treated in [investigator-initiated] studies across three oncology indications, we have reason to believe that our candidate may offer promising advantages for people living with rSLE,” Cao said.