CAR T-Cell Therapy From CRISPR Therapeutics Efficacious in CD19+ B-Cell Malignancies


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.

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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.

CRISPR Therapeutics reports positive results from its phase 1 CARBON Trial of CTX110™ in relapsed or refractory CD19+ B-cell malignancies. News release. CRISPR Therapeutics. October 12, 2021.
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