Novel CAR T Agent Granted FDA Orphan Drug Designation for Myeloma


GC012F, a duel target BCMA/CD19 CAR T-cell therapy was granted an orphan drug designation after durable responses were seen in a phase 1 study of the agent.

The FDA has granted an orphan drug designation to GC012F, a FasTCAR-enabled BCMA/CD19 dual targeted chimeric antigen receptor (CAR) T cell therapy for the treatment of multiple myeloma, according to a press release by Gracell Biotechnologies, Inc.

GC012F targets both malignant plasma cells expressing BCMA along with CD19-expressing early progenitor cells. This is meant to induce deep and durable responses in patients with multiple myeloma.

"As our lead candidate currently being developed on Gracell's FasTCAR next-day manufacturing technology platform, GC012F is a unique BCMA and CD19 dual-targeting CAR-T cell therapy," said Martina Sersch, MD, PhD, chief medical officer of Gracell, in a press release. "GC012F has demonstrated fast, deep and durable responses in patients with Relapsed/Refractory Multiple Myeloma in an ongoing IIT study in China with most patients on study being high risk according to mSMART 3.0 criteria, a difficult-to-treat patient population. We are very excited about being granted orphan drug designation for the treatment of multiple myeloma by the US FDA, another key milestone in advancing our program globally. Multiple myeloma patients are in need of more efficacious and tolerable therapies providing deep and durable responses and ultimately extending progression-free and overall survival."

The CAR T-cell therapy is currently being evaluated in a phase 1 study. The primary end point of the trial is the rate of incidence and severity of adverse events after GC012F infusion up to 24 weeks after infusion. Secondary end points include the percentage of patients with minimal residual disease 12 and 24 weeks after infusion, overall response rate (ORR), progression-free survival, duration of response, and overall survival.

During the study, all patients received a single infusion of GC012F at a dose of (1-5)10E5/kg cells.

According to the analysis, between October 2019 and July 2020, 19 heavily pretreated patients with multiple myeloma were given a single infusion of GC012F. The median number of prior lines of therapy was 5 (range, 2-9). At a data cutoff of January 12, 2012, 19 patients were evaluated for response. The ORR was 94.7%. One hundred percent of patients saw a reduction of paraprotein, with 18 of the 19 patients experiencing a 100% reduction.

In terms of safety, grade 1/2 cytokine release syndrome was seen in 84.2% of patients and grade 3 in 10.5% of patients. No grade 4/5 cytokine release syndrome was observed. Two deaths were observed over the course of the study. However, neither were found to be related to study treatment.

In order to participate in the study, patients must have a confirmed diagnosis of relapsed/refractory multiple myeloma a life expectancy of 3 more or more, adequate liver, kidney, and cardiopulmonary function, and have received at least 2 prior lines of therapy and be refractory to both an immunomodulatory drug and a proteasome inhibitor. Patients with other uncontrolled malignancies, convulsion or stroke within the past 6 months, clinical evidence of dementia, or who have pulmonary fibrosis are not eligible to participate.

1.Gracell Biotechnologies granted FDA orphan drug designation for FasTCAR-enabled BCMA/CD19 dual-targeting CAR-T Cell therapy candidate gc012f for the treatment of multiple myeloma. News release. Gracell Biotechnologies. November 19, 2021. Accessed November 19, 2021.
2.BCMA and CD19 targeted fast dual CAR-T for BCMA+ refractory/relapsed multiple myeloma. Accessed November 19, 2021.
3.Jiang H, Dong B, Gao L, et al. Long-term follow-up results of a multicenter first-in-human study of the dual BCMA/CD19 Targeted FasT CAR-T GC012F for patients with relapsed/refractory multiple myeloma. J Clin Oncol.2021;39(15):8014. doi: 10.1200/JCO.2021.39.15_suppl.8014.
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