The investigational allogeneic CAR-T therapy P-BCMA-ALLO1 appears to be more effective following strong immunosuppressive preconditioning.
Pictured: 3D illustration of a T cell attacking a cancer cell/iStock, Meletios Verras
Poseida Therapeutics on Sunday presented the latest findings from the Phase I study of its investigational BCMA-targeting, allogeneic CAR-T candidate P-BCMA-ALLO1, highlighting high response rates in patients with relapsed/refractory multiple myeloma.
These data come from 33 heavily pretreated patients with at least four weeks of follow-up. Of these, 11 received either 500 mg/m2 or 1,000 mg/m2 of a cyclophosphamide preconditioning regimen and were dosed with 2 million cells of the investigational therapy. The remaining patients were given 300 mg/m2 cyclophosphamide before P-BCMA-ALLO1 treatment.
Results showed an 82% overall response rate (ORR) in patients who received the higher cyclophosphamide preconditioning doses.
Additionally, ORR reached 100% in the subgroup of these patients who had been previously treated with autologous CAR-T BCMA-targeted therapy, and in those who had not been exposed to BCMA-targeting bispecific T-cell engaging antibody therapy.
Poseida presented these results at the 65th Annual Meeting & Exposition of the American Society of Hematology.
According to Poseida’s press release on Sunday, the expansion and persistence of CAR-T cells in treated patients is “highly dependent” on prior conditioning with cyclophosphamide. In particular, P-BCMA-ALLO1 levels in the blood were “much higher” in those who were given the 500-mg/m2 and 1,000-mg/m2 cyclophosphamide regimen.
As a result, clinical response was “inferior” in patients who were preconditioned with 300-mg/m2 cyclophosphamide, though Poseida did not provide specific response data for this treatment group.
P-BCMA-ALLO1 is an allogeneic, or off-the-shelf, investigational CAR-T therapy that targets the BCMA protein, which is typically expressed on the surface of malignant plasma cells, thereby arresting their growth. P-BCMA-ALLO1 also contains a high percentage of stem cell memory T cells (TSCM), which could potentially boost its durability.
In August 2022, Roche paid $110 million up front and pledged up to $6 billion to collaborate with Poseida on the development of P-BCMA-ALLO1.
For its Sunday readout, Poseida also performed cellular kinetic analyses in two patients who showed high levels of CAR T-cell expansion. These studies revealed that the cells persisted and remained measurable in the peripheral blood of one patient for at least four weeks, and in the bone marrow of the other patient for at least six weeks.
Moreover, in both patients, the infused drug product differentiated following administration and produced a much more effector T cell–rich population, including a killer T cell subpopulation.
These findings represent “the first known publicly presented data set that provides clear clinical evidence supporting the hypothesis that TSCM cells are the ideal cell type for allogeneic CAR-T,” Kristin Yarema, president of cell therapy at Poseida, said in a statement.
Sunday’s data also add to the wealth of clinical data supporting CAR-T therapies, which recently also demonstrated therapeutic potential in autoimmune diseases, including lupus and myositis.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
