IASO Biotherapeutics’ CAR T-cell therapy gets fresh FDA support
US agency grants CT103A fast track, regenerative medicine designations
The U.S. Food and Drug Administration (FDA) has granted fast track and regenerative medicine advanced therapy designations to CT103A, IASO Biotherapeutics’ experimental CAR T-cell therapy for relapsed or refractory multiple myeloma (RRMM), the company announced.
These statuses complement the orphan drug designation the treatment received from the regulatory agency last year.
Providing regulatory and financial support, these designations are intended to expedite the development of treatments that have shown promise for serious, life-threatening, or rare diseases for which available treatments fall short.
“Leveraging its … innovative product pipeline [and] integrated manufactural and clinical capabilities, IASO aims to deliver transformative, curable and affordable therapies that fulfill unmet medical needs to the patients in China as well as around the world,” the company said in its announcement.
US trial of CT103A expected in May
Fast track designation enables a rolling review and qualification for accelerated approval and priority review. Rolling review means the company can submit sections of a regulatory application as they are ready, rather than waiting for every section to be complete before the application can be reviewed by the agency.
Accelerated, or conditional, approval is granted to treatments whose immediate availability fulfills an unmet medical need, provided that early evidence supports its benefits outweighing potential risks.
RMAT designation allows for early, close, and frequent interaction with the FDA. In the event of an accelerated approval, further clinical evidence required to confirm the therapy’s benefits and achieve a full approval may come from sources other than the traditional confirmatory clinical trial — typically saving time and resources.
CT103A has so far only been tested in myeloma patients in China, where it received breakthrough therapy status and is now under priority review. There, CT103A is being co-developed by IASOÂ and Innovent Biologics.
In December, the FDA approved an investigational new drug application from IASO that allowed CT103A to enter clinical trials in the U.S.
An IASO-sponsored Phase 1b clinical trial (NCT05698303) is planned to evaluate the treatment’s safety and efficacy in up to 12 adults with RRMM. The study will be conducted at the University of Texas MD Anderson Cancer Center in Houston, Texas, and is estimated to start in May.
Chimeric antigen receptor (CAR) T-cell therapy works by using T-cells, a type of immune cell with the ability to fight cancer, to identify and target cancer cells more effectively.
The approach essentially involves collecting a patient’s T-cells and modifying them in the lab to produce a receptor, or CAR, that recognizes specific proteins on cancer cells. When infused back into the body, these engineered cells are expected to identify and eliminate cancer cells, while leaving the body’s healthy cells unharmed.
CT103A specifically targets a cancer protein called B-cell mature antigen (BCMA). It also contains a human antibody fragment that’s intended to reduce the risk of immune responses against the therapy — a common problem with CAR T-cell therapies that can limit their ability to be re-dosed if a person relapses.
An early pilot Phase 1 trial (ChiCTR1800018137) in China found the treatment to be safe among 18 RRMM patients, with all participants achieving a response to treatment after about a year. Nearly three-quarters (72.2%) showed a complete response or better, meaning their tumor was effectively eliminated.
To date, IOSA’s CAR T-cell therapy only tested in China
A subsequent Phase 1/2 trial, called FUMANBA-1 (NCT05066646), was launched to evaluate the safety and efficacy of CT103A in up to 132 adults with RRMM in China.
Interim data were presented last year at the European Hematology Association Research Conference in a presentation titled “Updated Phase 1/2 Data of the Safety and Efficacy of CT103A，Fully-Human BCMA-Directed CAR-T Cells in Relapsed/Refractory Multiple Myeloma.”
As of Jan. 21, 2022, 79 patients were treated with CT103A, with a median follow-up time of nearly 10 months.
These patients had received a median of five prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and a CD38 inhibitor. Among them, 12 (15.2%) had received previous non-human BCMA-targeted CAR-T cell therapy.
Results showed that most patients (94.9%) achieved at least a partial response to treatment after a median of 16 days. This included 89.9% of patients who attained a very good partial response or better, and 68.4% who achieved a complete response or better.
The treatment was similarly effective among 10 participants with extramedullary myeloma, in which the cancer grows outside of the bone marrow. All of these patients responded to treatment and 90% achieved a complete response or better.
Among the 12 people with previous exposure to CAR T-cell therapy, the response rate was 75%, with 41.7% of patients attaining a complete response or better.
Across the entire group of 79 patients, 92.4% were also negative for minimal residual disease, or the small number of cancer cells that sometimes remain after treatment and may cause disease relapse.
CT103A demonstrated a favorable and manageable safety profile.
Most patients (94.9%) experienced cytokine release syndrome, a potentially serious immune response commonly observed with CAR T-cell therapies. However, these reactions were usually mild or moderate and lasted a median of five days.
Immune effector cell-associated neurotoxicity syndrome, a type of serious immune response affecting the nervous system, was observed in two people, in whom symptoms were mild or moderate and were resolved.
CT103A generally did not lead to anti-treatment immune responses, with 16.5% of patients testing positive for antibodies against CT103A.
A Phase 1 FUMANBA-2 trial (NCT05181501) is investigating the potential benefit of CT103A in up to 20 newly-diagnosed, high-risk multiple myeloma patients.
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