FDA Clears Application for First Off-the-Shelf CAR T in Multiple Myeloma
The first off-the-shelf CAR T targeting BCMA has received FDA clearance to begin clinical trials. This week the FDA approved an investigational new drug application (IND) for the CAR T therapy called P-BCMA-ALLO1.
The new treatment is an allogeneic (donor T cell) therapy. When donor T cells are used, there is always the potential for the development of graft vs. host disease (GVHD). GVHD is when the patient's body starts rejecting the donor's cells and can lead to severe side effects. In an effort to reduce GVHD for this treatment, a high percentage of healthy donor stem cell memory T cells have been genetically edited to knock out the T-cell receptor and major histocompatability complex-1 to improve the compatibility between the tissues of different individuals.
Having the IND allows Poseida Therapeutics to begin the clinical trial enrollment process to evaluate the new treatment in relapsed or refractory multiple myeloma. In the Phase I dose escalation and safety study, patients will receive a pre-conditioning treatment and then will receive a single dose of P-BMCA-ALLO1. The trial will begin with a 3+3 dose escalation portion to determine the maximum tolerated dose and identify any dose-limiting or severe side effects.
Poseida also has an autologous CAR T product (P-BCMA-101) which is currently in a Phase II clinical trial.
The rationale to use a donor's T cells instead of the patient's own T cells is that the patient's T cells may not be sufficiently strong enough to combat the myeloma. They could be "exhausted" by the myeloma or prior myeloma therapy.
The company has proprietary technology that enables it to produce a large number of doses during a single manufacturing run. This allows the company to reduce costs and make the product available to more patients.
Benefits of having an off-the-shelf option for CAR T therapy include not only the potential strength of the T cells, but the speed of the treatment. An off-the-shelf option eliminates the 4-8 week manufacturing process, which can be a great challenge for patients with rapidly growing myeloma.
We look forward to seeing options like these enter clinical trials for multiple myeloma patients. Now that the technology has expanded, the research community is working to improve the impact and durability of these therapies.