CD19 CAR T CTX110 Yields Positive Results in B-Cell Malignancies in Ongoing Phase 1 Trial


Findings from the phase 1 CARBON trial indicated that patients with relapsed/refractory CD19-positive B-cell malignancies may benefit from CTX110 CAR T-cell therapy.

CTX110, a donor-derived gene-edited allogeneic CD19 CAR T-cell product, yielded positive results in a population of patients with relapsed/refractory CD19-positive B-cell malignancies who were treated in the ongoing phase 1 CARBON trial (NCT04035434), according to a press release from CRISPR Therapeutics.

Patients treated with a single dose of the off-the-shelf CAR T product at dose level 2 (100 x 106) and above experienced an overall response rate (ORR) of 58%, including a complete response (CR) rate of 38%. Notably, patients with large B-cell lymphoma (LBCL) experienced a 6-month CR rate of 21% and had the longest ongoing responses over 18 months following their initial transfusion. The response rates and durability observed on the trial were similar to other approved autologous CD19-targeting CAR T-cell therapies on an intent to treat basis.

“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,” Samarth Kulkarni, PhD, chief executive officer at CRISPR Therapeutics, said in a press release. “Furthermore, 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.”

The multicenter, open-label CARBON trial evaluated the safety and efficacy of CTX110 in adult individuals with CD19-positive disease who had received 2 previous lines of the therapy. Enrollment criteria for the clinical trial included those with aggressive disease presentation such as large B-cell lymphoma, not otherwise specified, high-grade double- or triple-hit lymphomas, and transformed follicular lymphoma.

Most patients had stage IV disease and were refractory to the last line of therapy prior to enrolling. A total of 9 patients were previously given autologous stem cell transplant. Those who had previously received autologous CAR T-cell therapy were not eligible.

Investigators reported that a total of 30 patients with LBCL enrolled on the study as of the data cut off of August 26, 2021, 26 of whom were treated with CTX110 with a minimum of 28 days of follow up. One patient did not receive treatment and 3 others were not evaluable as of the data cut off.

Those who were treated received a single CTX110 infusion after 3 days of receiving a standard lymphodepletion regimen, which included 30 mg/m2 of fludarabine and 500 mg/m2 of cyclophosphamide daily. Re-dosing with CTX110 was possible following disease progression.

The study’s primary end points were safety and ORR with key secondary end points including CR rate, duration of response, and overall survival.

In terms of safety, CTX110 was well tolerated across all dose levels. No cases of graft-versus-host disease or infusion reactions related to lymphodepletion or CTX110 were reported. All instances of cytokine release syndrome (CRS) were grade 1 or 2 and either did not required intervention or resolved following standard CRS management.

One case of grade 3 immune effector cell–associated neurotoxicity syndrome (ICANS) was reported in a patient with concurrent HHV-6 encephalitis. No further cases of ICANS were reported in patients who were being treated at dose levels 3 through 4. Moreover, 2 patients experienced grade 3 or higher infections, 1 being in the aforementioned patient with HHV-6 encephalitis and the other developing pseudomonal sepsis that resolved in 4 days.


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. Accessed October 13, 2021.

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