Enrollment in the CARBON trial has so far focused on aggressive disease such as diffuse B-cell lymphoma.
CTX110 seems to be well-tolerated and efficacious in patients with relapsed or refractory CD19+ B-cell malignancies, according to updated data from the phase 1 CARBON trial (NCT04035434) announced by CRISPR Therapeutics.
A single infusion of the allogeneic chimeric antigen receptor (CAR) T-cell therapy at dose level 2 (100x106 cells) and above yielded an overall response rate (ORR) of 58% and a complete response (CR) rate of 38% in patients with large B-cell lymphoma (LBCL). These responses were durable, with a 6-month CR rate of 21% and the longest response ongoing at over 18 months post-treatment.
“We are excited to share positive data from our CARBON trial, which show that CTX110 could offer patients with large B-cell lymphomas an immediately available ‘off-the-shelf’ therapy with efficacy similar to autologous CAR-T and a differentiated safety profile,” said Samarth Kulkarni, PhD, chief executive officer, CRISPR Therapeutics, in a statement.
The open-label, multicenter CARBON trial is evaluating CTX110 in patients with B-cell CD19+ malignancies that have received at least 2 lines of therapy. The trial’s primary end points are safety, including dose-limiting toxicities (DLTs), and ORR. Secondary end points include CR, duration of response, and overall survival.
The trial, which is ongoing, has enrolled 30 patients with LBCL, 26 of which have been treated with CTX110 with at last 28 days of follow-up and included in the data cutoff. One enrolled patient that was not treated with the cell therapy and 3 patients that had less than 28 days of follow-up were not included in the analysis. All patients completed 3 days of a standard lymphodepletion regimen before CTX110 treatment: fludarabine (30mg/m2/day) and cyclophosphamide (500mg/m2/day). Patients are able to be re-dosed with CTX110 following disease progression.
The trial has so far focused enrollment on those with aggressive disease, including diffuse LBCL, not otherwise specified (NOS), high-grade double- or triple-hit lymphomas, and transformed follicular lymphoma. Most patients had stage 4 lymphoma and were refractory to the last line of therapy prior to the trial. Nine patients received prior autologous stem cell transplant but patients who received prior autologous CAR-T therapy were not eligible.
No grade 3 or higher cytokine release syndrome (CRS) and low rates of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and infection give CTX110 a positively differentiated safety profile compared to other CAR T-cell therapies. No Graft versus Host Disease (GvHD) or infusion reactions were observed.
Grades 1 and 2 CRS did occur but resolved either without specific intervention or with standard CRS management. Patients re-dosed with CTX110 did not experience more frequent or severe CRS. One patient did experience at least a grade 3 ICANS with concurrent HHV-6 encephalitis, which CRISPR Therapeutics previously disclosed. No other patients treated at dose levels 3 and 4 experienced ICANS. One other patient developed at least a grade 3 infection of pseudomonal sepsis which resolved in 4 days.
CRIPSR Therapeutics plans to expand CARBON into a registrational trial with consolidation dosing in the first quarter of 2022.
“We have the potential to improve upon already observed efficacy with a consolidation dosing strategy. Based on these encouraging results, we are planning to expand CARBON into a potentially registrational trial in the first quarter of 2022,” Kulkarni added.