Bellicum Pharma has the first data on BPX-601, its first CAR-T with a built-in activation switch to boost its effects, and says initial results show signs of biologic activity.

Data from 12 patients enrolled in a phase 1/2 dose-escalation study in PSCA-positive metastatic pancreatic cancer treated with the CAR-T showed that out of six evaluable patients, four had stabilized disease, with two seeing tumor shrinkage of at least 20%. More importantly, however, the results suggest BPX-601 is working as intended.

The PSCA-targeting therapy is designed to activate in the body after patients are dosed orally with a small-molecule drug called rimiducid. In patients who weren’t given the drug, there was only a limited expansion of the CAR-T cells and little persistence in the body. However, a single dose of rimiducid given to four patients seven days after BPX-601 caused cell numbers to expand between three- and twentyfold and persist for at least three weeks.

It’s a preliminary readout, but it suggests the activation mechanism for BPX-601 and follow-up CAR-Ts is working. Now, the big test is to see if that translate to a therapeutic advantage—Bellicum reckons that activation should enable the CAR-T to override immune inhibitory mechanisms, including the PD-1 and TGF-beta pathways.

Emboldened by the early readout, Bellicum says it is now adding additional tumor types to the trial and moving ahead with plans for repeat rimiducid dosing to extend the activation phase of treatment.

The safety profile of BPX-601 also looks clean so far, with no cases of the cytokine-release syndrome (CRS) and neurotoxicity that have been an issue with some other CAR-Ts.

The BPX-601 trial was being designed when CRS-related deaths were being reported with Juno’s now-abandoned JCAR015, and speculation that the conditioning regimen used to prepare the immune system to receive the CAR-T—and specifically a drug called fludarabine—was at fault.

For that reason, Bellicum’s trial only used cyclophosphamide to condition patients, which may not have created the best environment to allow the CAR-Ts to flourish. Now—in light of the greater knowledge of how to avert and manage CRS—it plans to add fludarabine back into the conditioning regimen.

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