Bellicum Pharma has the first data on BPX-601, its first CAR-T with a built-in activation change to spice up its results, and says preliminary outcomes present indicators of biologic exercise.
Data from 12 sufferers enrolled in a section 1/2 dose-escalation examine in PSCA-positive metastatic pancreatic most cancers handled with the CAR-T confirmed that out of six evaluable sufferers, 4 had stabilized illness, with two seeing tumor shrinkage of at the very least 20%. More importantly, nevertheless, the outcomes counsel BPX-601 is working as meant.
The PSCA-targeting remedy is designed to activate within the physique after sufferers are dosed orally with a small-molecule drug referred to as rimiducid. In sufferers who weren’t given the drug, there was solely a restricted growth of the CAR-T cells and little persistence within the physique. However, a single dose of rimiducid given to 4 sufferers seven days after BPX-601 induced cell numbers to broaden between three- and twentyfold and persist for at the very least three weeks.
It’s a preliminary readout, nevertheless it suggests the activation mechanism for BPX-601 and follow-up CAR-Ts is working. Now, the massive check is to see if that translate to a therapeutic benefit—Bellicum reckons that activation ought to allow the CAR-T to override immune inhibitory mechanisms, together with the PD-1 and TGF-beta pathways.
Emboldened by the early readout, Bellicum says it’s now including extra tumor varieties to the trial and transferring forward with plans for repeat rimiducid dosing to increase the activation section of remedy.
The security profile of BPX-601 additionally seems clear up to now, with no instances of the cytokine-release syndrome (CRS) and neurotoxicity which were a problem with another CAR-Ts.
The BPX-601 trial was being designed when CRS-related deaths have been being reported with Juno’s now-abandoned JCAR015, and hypothesis that the conditioning routine used to organize the immune system to obtain the CAR-T—and particularly a drug referred to as fludarabine—was at fault.
For that cause, Bellicum’s trial solely used cyclophosphamide to situation sufferers, which can not have created the very best atmosphere to permit the CAR-Ts to flourish. Now—in gentle of the better data of the best way to avert and handle CRS—it plans so as to add fludarabine again into the conditioning routine.