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.

The intended goal of the dual CAR T is to treat mature myeloma cells (by targeting BCMA) and potentially myeloma precursor cells (by targeting CD19). In prior studies, just targeting CD19 has not worked in multiple myeloma, because it is not present on mature myeloma cells.

A study started in 2015 by UPENN researchers hypothesized that the use of auto transplant followed by a T cell therapy targeting CD19 called CTL019 would extend remissions. They found that the transplant plus CTL019 was safe and feasible without severe cytokine release syndrome. Two of the 10 patients had significantly longer progression free survival compared to transplant alone. It will be interesting to see follow-up data from the Gracell study with the combined targets.

This is not the first Chinese company to provide a CAR T therapy - Legend Bio partnered with Janssen Oncology to produce cilta-cel, a BCMA-directed CAR T treatment.