ASH: Another 'off-the-shelf' cell therapy leader shows durability issues, raising renewed concerns about emerging field
The next generation of cell therapies have focused in large part on the development of allogeneic — better known as “off-the-shelf — drugs that can cut manufacturing times and hopefully evade a patient’s immune system. One of the early players in that race has new data at #ASH21 that show deep responses but will also raise fresh concerns about these therapies’ durability.
Precision Biosciences’ PBCAR0191, a CD19-directed allogeneic CAR-T cell therapy, posted a complete response rate of 59% in 22 heavily pretreated patients with various forms of relapsed or refractory non-Hodgkin’s lymphoma and acute lymphocytic leukemia, six of whom had previously received an autologous CAR-T before dosing, the biotech said.
At a Nov. 16 data cutoff, PBCAR0191 spurred an overall response rate of 73% in that early Phase I/II cut, well in line with current-generation CAR-Ts, but durability concerns in this data set will likely raise eyebrows on Precision’s chance to upset current CAR-T and renew concerns about the field on the whole.
Among the 17 evaluable NHL patients in this study, most responders relapsed before hitting the six-month mark, shutting down the drug’s chances as a one-time infusion for most patients.
On the safety front, PBCAR0191 posted no serious cytokine release syndrome events and just one Grade 3 neurotoxicity side effect. There was one infectious death that investigators said was possibly related to treatment.
It’s a result that mirrors readouts from Precision’s nearest competitors Allogene and CRISPR Therapeutics, both of which previously uncorked data for their own allogeneic CAR-Ts showing questions over durability. Precision did tout data in a small cohort of patients who had previously received an autologous CAR-T, saying their durability of response was longer than on that prior therapy, but it’s hard not to see PBCAR0191’s underwhelming results as an appetizer into Precision’s move into even more next-gen tech with a “stealth” CAR-T dubbed PBCAR19B.
Precision uncorked very early Phase I data for that drug this weekend too, which uses gene editing to knock down beta-2 microglobulin, an MHC molecule that triggers a graft vs. host response, and insert an HLA-E transgene to evade rejection from patients’ natural killer cells.
A Phase I study in relapsed/refractory NHL is enrolling now, and Precision expects data by the middle of next year, CMO Alan List said in a statement.
Meanwhile, this weekend Precision also rolled out new data for its allogeneic BCMA-directed CAR-T candidate PBCAR269A showing the drug couldn’t top autologous CAR-T in terms of efficacy in a Phase I/IIa trial. Precision will now push a combination approach with this drug alongside nirogacestat, a gamma secretase inhibitor from SpringWorks Therapeutics, with data expected by the middle of next year.