Dual Myeloma CAR T Targeting BCMA and CD19 Gets FDA Orphan Drug Designation

China-based Gracell Biotechnologies was recently given FDA Orphan Drug designation for a dual CAR T targeting BCMA and CD19 in multiple myeloma. Using different technology to solve some of the issues of autologous CAR T therapies, the FasTCART platform will be used to move GC012F through the clinical trial process. Studies of GC012F are currently in Phase I trials. 

According to the company, CAR T cells manufactured on the FasTCAR platform appear younger, less exhausted and are better at proliferating and persisting. The company touts next-day manufacturing which would improve cell production efficiency with potential to make the treatment less expensive and more accessible. 

Study results from the Phase I were presented at ASCO 2021 showing: 

• As of January 12, 2021, the study had enrolled and treated 19 patients at three dose levels with the highest dose level of 3x10⁵ cells per kg. Additional patients were treated since last update (reported at ASH 2020) in the highest dose level.
• Early Overall Response Rate (ORR) shows a promising 94.7% (18/19) with all responses being VGPR or better (sCR), demonstrating fast, deep and durable responses in all dose levels.
• 100% of the patients treated at the highest dose level (n=9) obtained MRD negative sCR.
• 18 of the 19 patients (94.7%) treated were classified as high-risk according to mSMART 3.0 guidelines and patients had received a median of 5 prior lines of therapy.
• 94.7% (18/19) of the patients were triple exposed to a PI, IMiD, and at least a third treatment modality, including anti-CD38 targeted therapy.
• The safety profile of GC012F was consistent with previous findings with mostly low grade of cytokine release syndrome (CRS) (84% Grade 1/2, 11% (n=2) patients Grade 3). No Grade 4 or 5 CRS and no ICANS (immune effector cell-associated neurotoxicity) were observed in any of the 19 patients. Treatment-emergent adverse events (TEAEs) presented predominantly as cytopenias and AST increase. All TEAEs resolved with standard therapy.
• Patients are continued to be followed for efficacy and safety.

GC012F is currently being evaluated in investigator-initiated trials in China, including in newly diagnosed multiple myeloma patients. The company is partnering with a company called Lonza to support US-based manufacturing.