New CAR T-Cell Therapy Appears Safe in B-Cell Malignancies

CTX110, an allogeneic chimeric antigen receptor (CAR) T-cell therapy for the treatment of relapsed or refractory CD19-positive B-cell malignancies, is well tolerated across a variety of dosing levels, according to results of the phase 1 CARBON (NCT04035434) study released by CRISPR Therapeutics.¹

“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 of CRISPR Therapeutics, 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 phase 1 CARBON study has an estimated enrollment of 143 participants and an estimated study completion date of August 2026. The primary end point of the dose escalation portion is the rate of adverse events (AEs). The primary end point of the dose expansion cohort is objective response rate (ORR). Secondary end points include duration of response, duration of clinical benefit, and progression-free survival.²

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During the study, patients received a single transfusion of CTX110 following 3 days of a standard lymphodepletion regimen. The regimen contained fludarabine 30mg/m2 a day and cyclophosphamide 500mg/m2 a day. At disease progression, patients were eligible for redosing. 

At the August 26, 2021 data cutoff, 30 patients with large B-cell lymphoma (LBCL) had been enrolled, 26 of which had received the agent with at least 28 days of follow-up. Only patients with at least 28 days of follow-up were included in the analysis.

The ORR was 58% and the complete response rate (CR) was 38% in LBCL with a single dose of the agent at dose level 2 and above. The 6-month CR rate was 21%, and the longest response was still ongoing at 18 months after initial infusion. 

In terms of safety, no cases of graft versus host disease and no infusion reactions were reported. Only grade 1 or 2 cytokine release syndrome was observed. Other AEs included infections such as 1 case of pseudomonal sepsis and one case of grade 3 or higher immune effector cell-associated neurotoxicity syndrome. However, this was reported in a patient with concurrent HHV-6 encephalitis. 

In order to participate, patients must be at least 18 years of age, a confirmed B-cell malignancy, an ECOG score of 0 or 1, adequate renal, liver, cardiac, and pulmonary organ function, and agree to use acceptable methods of contraception. Patients who received previous CAR T-cell therapy, a history of central nervous system involvement, a seizure disorder, active HIV, a previous or concurrent malignancy, or a primary immunodeficiency disorder are not eligible to participate.

The study is currently recruiting in California, Florida, Georgia, Illinois, Kansas, Massachusetts, Minnesota, Missouri, New York, Oregon, Pennsylvania, Tennessee, Texas, Virginia, and Washington.

_REFERENCES:

_{1.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. https://bit.ly/3AHUaZj.}

_{2.A safety and efficacy study evaluating CTX110 in subjects with relapsed or refractory B-cell malignancies (CARBON). ClinicalTrials.gov. Accessed October 13, 2021. https://bit.ly/3j05om1.}