Gracell Biotechnologies Co., Ltd, a clinical-stage immune cell therapy company, announced the progressive clinical outcomes for leading product candidates FasTCAR-19, Dual CAR-19-22, and Dual CAR-BCMA-19 at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, held from December 7-10. Multiple pilot studies intend to evaluate the safety and efficacy of Gracell's first-in-class FasTCAR-19 (GC007F), Dual CAR-19-22 (GC012F) and Dual CAR-BCMA-19 (GC022F) cell therapy.
FasTCAR-19
FasTCAR-19 or GC007F uses Gracell's patented FasTCARTM solution, which genetically modifies a patient's T-cells to express CD19-specific chimeric antigen receptor (CAR) for the treatment of B-cell acute lymphoblastic leukemia (B-ALL).
Utilizing the unique bioprocessing, FasTCAR-19 cells can be produced overnight through viral transfection in use of Gracell's proprietary fully-closed manufacturing system (from apheresis to filling). These cells are considered far more potent and durable in comparison to current market alternatives. To date, all 37 patient samples have been successfully manufactured. The process has been proven efficient, stable and duplicable, with a median 36.8% (range 13.1%-70.3%) transfection success and a median copies of 0.95 (range 0.2-4.21).
As of November, this investigational study enrolled 37 adult and adolescent patients aged from 14 to 70 years, who suffered from r/r B-ALL and had failed to respond to multiple prior lines of therapy, from eight clinical centers. All patients received a single infusion of FasTCAR-19 at one of the three-dose level (low: 0.6*10^5/kg; mid: 1.0*10^5/kg, and high: 1.6*10^5/kg), followed by prior conditioning regimen of fludarabine-cyclophosphamide (FC).
The treatment efficacy was assessed in 35 patients over 28 days of follow-up, of which:
- 34 (97.1%) achieved a complete remission with or without complete blood count recovery (CR/CRi) on Day 28;
- 32 (91.4%) achieved minimum residual disease negative complete remission (MRD-CR);
During the over six month-durable remission period, FasTCAR-19 demonstrated a good level of persistence in line with previous clinical trials. In terms of safety, all 37 patients tolerated the single infusion of FasTCAR-19 at different dose levels, with no dose-limiting toxicities observed. The most common safety concerns were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) where mild to moderate side effects were observed. Across 30 patients in the low to mid doses group, only 5 (16.7%) manageable Grade 3 CRS and 5 (16.7%) manageable Grade 3 ICANS were reported; while the remaining 23 (76.7%) had Grade 1-2 CRS. The low to mid doses group will likely be selected for extensive study in future clinical trials.
Beyond single-antigen CAR, Dual CAR-T cells can deliver promising clinical outcomes
Single-antigen CAR-T cells have demonstrated considerable efficacy; however, antigen loss and high relapse rate have been observed in a significant number of patients. To combat this, treatments containing two separate CARs and dual transduction (GC022 targeting CD19 and CD22, GC012 targeting BCMA and CD19) were developed. Following positive results from in vitro and in vivo studies, human clinical trials have commenced testing the safety and feasibility of Dual CAR-19-22 and Dual CAR-BCMA-19 to treat B-ALL and MM, respectively.
Dual CAR-19-22
Dual CAR-19-22 or GC022 has achieved a manufacturing success rate of 20/20, without any patient loss due to manufacturing failure. Enrolled patients aged from 4-45 years old who has B-ALL, received a single infusion of Dual CAR-19-22 at one of the three-dose levels (low: 0.5*10^6/kg; mid: 2.0*10^6/kg, and high: 3.0*10^6/kg), under conventional bioprocessing. The study demonstrated a very good safety profile and high efficacy at mid to high doses.
The treatment efficacy was assessed in 20 patients with a 28-day follow-up, of which:
- 4 in the low dose group reported no response;
- 15 of 16 (93.8%) in mid and high dose groups achieved complete remission, and confirmed with MRD-CR, with or without complete blood count recovery (CR/CRi) on Day 28.
Dual CAR-19-22 proved effective on patients who had previously been treated...
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