Phase 1 CARBON Study Demonstrated Clinical Benefits with Allogeneic CAR-T Therapy CTX110 in Patients with R/R LBCL

Allogeneic chimeric antigen receptor T-cell (CAR-T) therapies may offer advantages over autologous CAR-T therapies, such as the potential for immediate “off-the-shelf” availability and no leukapheresis for patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). CTX110® is an investigational allogeneic CD19-directed CAR-T therapy engineered using CRISPR/Cas9 editing to disrupt the endogenous T-cell receptor (TCR) alpha constant (TRAC) locus to fully abrogate TCR expression and disrupt β2 microglobulin. CARBON (NCT04035434) is a phase 1, open-label, multicenter, global study evaluating the safety and efficacy of CTX110 in adult patients with R/R LBCL with ≥2 prior lines of therapy (LOTs); results from the dose-escalation phase of CARBON were presented at the 64th American Society of Hematology Annual Meeting and Exposition.

Key exclusion criteria for CARBON included prior CAR-T therapy and central nervous system involvement. Patients received standard lymphodepleting chemotherapy (LDC) with FluCy for 3 days, followed by CTX110; active doses of CTX110 ranged from 300 × 106 to 600 × 106 CAR T-cells. Patients could receive an additional infusion of CTX110 if they experienced initial benefit and subsequently progressed. A subset of patients with an initial day 28 response of stable disease or better were eligible for a second planned infusion on day 35. Primary end points included incidence of adverse events (AEs) and overall response rate (ORR, per Lugano 2014 criteria). Secondary end points included complete response (CR) rate, duration of response, and overall survival.

Thirty-four patients with LBCL were enrolled for dose escalation and 32 received CTX110. At baseline, median age was 64 years (range, 25-75), 47% of patients received ≥3 prior LOTs, and 34% received prior stem-cell transplantation. Many patients had high-risk features at baseline; 53% had refractory disease, 34% had bulky disease (defined as sum of the product [of perpendicular] diameters >50 cm2), and 53% had lactate dehydrogenase more than the upper limit of normal. Median time from enrollment to the beginning of LDC was 2 days. Among patients who received ≥1 infusion of CTX110 at doses of ≥300 × 106 CAR T-cells (N = 27), best ORR and CR rates were 67% (18/27) and 41% (11/27), respectively; the 6-month CR rate was 19% (5/27), and 3 patients have achieved and maintained ongoing CR beyond 24 months. For the 13 patients who received a second infusion of ≥300 × 106 CAR T-cells, T-cell expansion was observed in all patients, with no changes in the overall safety profile. Following CTX110 infusion, there was no graft-versus-host disease nor infusion reactions. Any-grade cytokine release syndrome (CRS) was reported in 56% of patients (18/32), with no grade ≥3 CRS. Any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) was reported in 9% of patients (3/32), including 2 cases of grade ≥3 ICANS. Grade ≥3 infections occurred in 12.5% of patients (4/32), including 1 patient who died with human herpesvirus-6 encephalitis. Seven patients experienced serious AEs attributed to CTX110, including CRS, ICANS, and febrile neutropenia.

In a heavily pretreated R/R LBCL patient population, CTX110 at doses of ≥300 × 106 CAR T-cells resulted in clinically meaningful ORR, CR rates, and durable remissions, accompanied by a favorable safety profile. Nearly half of all patients who achieved a CR maintained this response for ≥6 months. CTX110 offers a potential off-the-shelf treatment option, as median time from enrollment to drug infusion was 7 days. Administration of a second CTX110 infusion was well tolerated and demonstrated evidence of T-cell expansion. An expansion phase of the CARBON study is in progress.


McGuirk JP, Tam CS, Kröger N, et al. CTX110 allogeneic CRISPR-Cas9‒engineered CAR T cells in patients (patients) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL): results from the phase 1 dose escalation CARBON study. Presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Poster presentation 4629.

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