Complete Remission Induced in B-cell ALL Patients After Single Dose of FasT CAR-19 Therapy, Preliminary Data Show

A single infusion of an experimental cell therapy called FasT CAR-19 was well-tolerated and induced a complete remission in all B-cell acute lymphoblastic leukemia (B-ALL) patients included in a Phase 1 trial, the therapy’s developer, Gracell Biotechnologies, has announced.

All patients had received multiple prior lines of therapy before entering the trial, and 87% also achieved minimal residual disease negativity — that is, very low levels of leukemia cells in the bone marrow.

The findings were recently presented at the CAR-TCR Summit Asia in Shanghai. The talk, “FasT CAR: A Breakthrough Cell Therapy Technology for Malignancies,” was given by William Wei Cao, founder, chairman, and CEO of Gracell.

CAR T-cell therapy is a type of treatment that involves collecting a patient’s own immune T-cells and modifying them to produce a chimeric antigen receptor, or CAR, that targets a specific cancer protein. The genetically engineered cells are then expanded to millions in the lab and inserted back into the patient, where they help fight the tumor.

The problem with current approaches is that the manufacturing process is expensive and long, e.g., the time from collection to infusion can take up to three weeks, which may be too long for rapidly-growing diseases.

But Gracell has developed a platform, called FasT CAR-T (GC007F), that is less expensive and able to manufacture its CD19-targeting CAR T-cell product in a single day, as opposed to 14 days for conventional CAR T-cell therapies.

An early Phase 1 clinical trial (NCT03825718) is currently evaluating FasT CAR-19 in adolescent and adult patients in China, who have relapsed or refractory disease and failed to respond to multiple prior lines of therapy.

The trial is still recruiting participants, from 2 to 70 years old, and more information is available here. The multi-center trial has already included 19 B-ALL patients, age 14 to 70 years.

By the time of the analysis (June 12), all the patients had received a single injection of FasT CAR-19, given after a chemotherapy regimen that is meant to destroy cancerous B-cells while creating room for the newly injected cells.

Patients received one of three FasT CAR-19 doses. Because this treatment has shown a higher potency than other CAR T-cell products, the low and high dose corresponded to 3.3% and 10% of the standard doses of these other therapies, respectively.

Of the first 16 patients assessed for efficacy, all went into complete remission with or without complete blood-count recovery. The majority of the patients (94%) were still responding at the time of the analysis.

Fourteen patients (87%) also had negative minimal residual disease (MRD). Of note, a MRD-negative patient has fewer than one cancer cell per 10,000 cells in the bone marrow.

FasT CAR-19 was well-tolerated at the different doses, with no dose-limiting toxicities detected. Cytokine release syndrome — a form of systemic inflammatory response causing flu-like symptoms — and neurotoxicity were the most common adverse effects detected, although they were mild (in the low-dose group) or moderate in intensity.

“We are very excited to see that the patients with relapsed or refractory B-ALL in this study gained substantial clinical benefit from FasT CAR-19,” Cao said in a press release.

“Although the potential of FasT CAR technology is yet to be unlocked, the results of this study have enhanced our confidence to move on with dose expansion studies and to apply FasT CAR to products for various indications, including multiple myeloma and non-Hodgkin lymphoma,” he added. “We are eager to see Gracell’s highly efficacious, but affordable FasT CAR-T therapies benefit patients globally.”