Off-the-Shelf CAR T-Cell Product CTX100 Promising in Relapsed/Refractory CD19+ B-Cell Malignancies


The investigational wholly-owned allogeneic chimeric antigen receptor T-cell therapy CTX110 demonstrated dose-dependent efficacy and responses in patients with relapsed/refractory CD19-positive B-cell malignancies.

Joseph McGuirk, DO

Joseph McGuirk, DO

The investigational wholly-owned allogeneic chimeric antigen receptor (CAR) T-cell therapy CTX110 demonstrated dose-dependent efficacy and responses in patients with relapsed/refractory CD19-positive B-cell malignancies, according to topline results from the phase 1 CARBON trial (NCT04035434).

Findings showed that at 3 months, the complete response (CR) rate was 50% out of the 4 patients enrolled at the dose level 3 cohort of the study. Both responders currently remain in CR.

"From this early data read-out, CTX110 has shown dose-dependent efficacy and response rates that are comparable to the early autologous CAR-T trials,” study investigator Joseph McGuirk, DO, professor of medicine, division director of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Medical Center stated. “Furthermore, CTX110 had an acceptable safety profile, which could make CAR-Ts more widely accessible.”

CRISPR Therapeutics, the developer of the CAR T-cell product, stated that the trial continues to enroll patients.

In the open-label, multicenter study, investigators are evaluating the efficacy and safety of CTX110 in adult patients with relapsed/refractory non-Hodgkin lymphoma who have received at least 2 prior lines of therapy. As of the data cutoff date, which is September 28, 2020, 12 patients were enrolled and had been infused with the CTX110 therapy.

Patients are infused with CTX110 following 3 days of lymphodepletion using 30 mg/m2 of daily fludarabine and 500mg/m2 of daily cyclophosphamide. Dosages were differed across 4 cohorts: 30 x 106 (dose level 1; n = 3), 100 x 106 (dose level 2; n = 3), 300 x 106 (dose level 3; n = 4), and 600 x 106 (dose level 4; n = 1).

The primary end points are safety, which is measured by the incidence of dose-limiting toxicities (DLTs), and overall response rate. Key secondary end points include duration of response, progression-free survival, and overall survival.

The topline data comprise the 11 patients who had completed their 1-month assessment as of the data cutoff date. Moreover, a disease assessment was performed by centralized independent radiological review, according to the 2014 Lugano response criteria.

The safety data overview comprised 10 patients at dose levels 1 to 3 and 1 patient at dose level 4. In the primary cohort, no DLTs were observed, and there were no cases of graft-versus-host disease, although there were high HLA-mismatch between allogeneic CAR T-cell donors and patients. Additionally, no infusion reactions to either chemotherapy or to CTX110 were reported. Cytokine release syndrome (CRS) was identified in 3 patients, each of which was grade 2 below; all cases were resolved with tocilizumab (Actemra).

One patient in this cohort experienced grade 2 immune effector cell—associated neurotoxicity syndrome, which did improve within 24 hours of standard interventions. After infusion, periorbital cellulitis and febrile neutropenia were reported as serious adverse events; both of these were resolved and were not related to either disease progression or CTX110.

In the dose level 4 cohort, the patient experienced grade 2 CRS on day 5, which resolved in 5 days. On day 25, the PET/CT assessment showed that the patient had achieved a CR.

The following day, this patient was hospitalized with febrile neutropenia and developed symptoms of short-term memory loss and confusion, which later progressed to obtundation that required intubation. The patient did not respond to initial treatment, and was later found to have reactivation of HHV-6 and HHV-6 encephalitis and received antiviral therapy. Supportive care was withdrawn, and the patient died 52 days following CTX110 treatment.

Regarding efficacy in the 11 patients, 1 CR (33.3%) was achieved at the dose level 2 cohort, 2 (50%) at the dose level 3 cohort, and 1 (100%) at the dose level 4 cohort.

The 4 patients with CR had deep responses, including complete resolution of extranodal disease, normalization of all nodal disease to 1.5 cm or smaller, and a Deauville score of 2 or lower. One of these patients, who had 30% lymphoblasts in the bone marrow, had full clearance after CTX110 infusion.

The CRs were achieved both in patients with diffuse large B-cell lymphoma and with transformed follicular lymphoma, as well as in those who were primary refractory and who had relapsed after autologous stem cell transplant.

CTX110 was detected at multiple time points in all patients at the dose level 2 cohort and above; the peak expansion occurred at 1 to 2 weeks, and cells were spotted as late as 180 days following infusion​.

“We are highly encouraged by today’s data, which demonstrate the promise of allogeneic therapies in treating hematological malignancies,” Samarth Kulkarni, PhD, chief executive officer of CRISPR Therapeutics, the developer of the CAR T-cell product. “Over time, we believe CRISPR-edited allogeneic CAR-T has the potential to leapfrog autologous CAR-T and benefit much broader patient populations.

McGuirk concluded that while longer follow-up is required for these data, the early findings do support the potential for CTX110 to become an effective off-the-shelf CAR-T therapy for patients with relapsed/refractory B-cell malignancies.

Additional allogeneic CAR-T programs the company has in their pipeline include CTX120 and CTX130.


CRISPR Therapeutics reports positive top-line results from its phase 1 CARBON Trial of CTX110™ in relapsed or refractory CD19+ B-cell malignancies. News release. CRISPR Therapeutics. October 21, 2020. Accessed October 23, 2020.

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