Data from a phase 1/2a study showed notable response rates in patients who had received a median of 5 prior lines of therapy.
An investigational CD19-directed chimeric antigen receptor (CAR) T-cell therapy, PBCAR0191, has generated a 100% objective response rate in an ongoing phase 1/2a clinical trial, according to an announcement from Precision BioSciences.
The allogeneic, potentially first in class cell therapy is being explored in patients with aggressive lymphomas who relapsed following autologous CAR T-cell therapy.
"We believe this data is timely and highly relevant. By 2025 the number of autologous CAR T relapsed patients is expected to grow 4- to 5-fold based on data from late 2021 that advanced autologous CAR T into the second line diffuse large B-cell lymphoma (DLBCL) setting," said Michael Amoroso, chief executive officer, Precision BioSciences, in a statement. "Today, patients who relapse after CAR T treatment remain highly underserved with no approved standard of care and a progression free survival of only 1 to 2 months.”
As of the May 31 data cutoff, Precision reported continued positive efficacy in its 11 evaluable participants in the ASH and New cohorts who received PBCAR0191 Dose Level (DL) 3 with enhanced lymphodepletion (3 × 10 cells/kg with fludarabine 30 mg/m2/day × 4 days + cyclophosphamide 1000 mg/m2/day × 3 days) and PBCAR0191 DL4b with decreased lymphodepletion (500 × 10 cells (flat dose) with fludarabine 30 mg/m2/day × 4 days + cyclophosphamide 750 mg/m2/day × 3 days), respectively.
Across both cohorts, a 100% ORR was observed, including a 73% complete response rate and a 50% durable response rate greater than 6 months. Six participants have ongoing durable responses up to 18 months. Among the ASH cohort, 50% had a response duration greater than 6 months. In the New cohort, all 5 evaluable participants reached complete response.
Notably, no cytokine release syndrome grade 3 or higher was observed in either cohort. Two cases of grade 3 immune effector cell-associated neurotoxicity syndrome were recorded across the cohorts, though both cases resolved to grade 1 within 24 to 48 hours; and 2 grade 5 events associated with late occurring encephalopathy suspected to be related to fludarabine-associated neurotoxicity were reported in the New cohort; and no cases of graft versus host disease were reported in either group. Notably, one participant in the New cohort died on day 23 due to suspected fludarabine-associated neurotoxicity despite reaching a complete response on Day 21 confirmed by imaging.
In addition, investigators noted that infections grade 3 or higher occurred less often in the New cohort (1/6, 17%) compared with the ASH cohort (4/6, 67%).
Precision pointed out that their manufacturing process has yeilded an improved CAR T product that allows for less lymphodepletion, ultimately affecting hematologic recovery.
In addition, "the cell expansion observed with PBCAR0191 cells at DL4b with lower dose lymphodepletion—the New Cohort—matched the median autologous CAR T peak expansion in subjects who achieved a long durable response in the ZUMA-1 trial. We believe this to be a first for allogeneic CAR T therapy studied in any population (earlier lines or more heavily pre-treated)," added Precision chief medical officer Alan List, MD.
Dosing will continue in the trial, which plans to continuously reduce the lymphodepletion dose over time. Further updates on the study and status of product development are expected closer to the end of the year.