CRISPR-edited allogeneic CAR-T demonstrates activity in advanced lymphoma


CTX110 exhibited clinical activity among patients with advanced B-cell lymphoma, according to topline data from a phase 1 dose-escalation trial released by the agent’s manufacturer.

Researchers reported dose-dependent responses to the investigational chimeric antigen receptor T-cell therapy. The agent also exhibited an acceptable safety profile at all but the highest of four evaluated doses.

CTX110 (CRISPR Therapeutics) is an allogeneic, CD19-targeted, CRISPR/Cas9 gene-edited CAR T-cell therapy designed to treat CD19-positive B-cell malignancies.

“From this early data readout, 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 and division director of hematologic malignancies and cellular therapeutics at University of Kansas Medical Center, said in a CRISPR Therapeutics-issued press release.

“Furthermore, CTX110 had an acceptable safety profile, which could make CAR-Ts more widely accessible,” McGuirk added. “[Although] longer follow-up is required, these early data support the potential for CTX110 to become an effective off-the-shelf CAR-T therapy for patients with relapsed or refractory B-cell malignancies.”

The phase 1, open-label, multicenter CARBON trial evaluated the safety and efficacy of CTX110 for adults with relapsed or refractory non-Hodgkin lymphoma who received at least two prior lines of therapy.

Twelve patients have enrolled so far. Topline results were based on 11 patients who completed a 1-month follow-up assessment by the data cut-off date of Sept. 28.

Patients completed a 3-day course of lymphodepletion and then received IV infusions of CTX100 at one of four dose levels — 30×106 (dose level 1, n = 3), 100×106 (dose level 2, n = 3), 300×106 (dose level 3, n = 4) or 600×106 (dose level 4, n = 1) CAR T cells.

Safety —determined by incidence of dose-limiting toxicities — and overall response rate served as primary endpoints. Duration of response, PFS and OS served as secondary endpoints.

Researchers reported no dose-limiting toxicities and no cases of graft-versus-host disease among the 10 patients who received the three lowest doses.

Three (30%) of these patients developed grade 2 or lower cytokine release syndrome, and all cases resolved with tocilizumab (Actemra, Genentech). One patient developed grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) that improved within 24 hours of standard interventions.

Three (30%) of these patients — one who received dose level 2 and two who received dose level 3 — achieved complete response. The two patients who achieved complete response at dose level 3 remained in complete response at data the time of analysis.

The lone patient who received the highest dose level developed grade 2 cytokine release syndrome 5 days after CTX110 infusion, but it resolved within 5 days.

PET/CT at day 25 showed the patient achieved complete response, but he was hospitalized the next day with febrile neutropenia, later exhibited confusion and short-term memory loss, and eventually required intubation due to significant obtundation.

The patient received steroids, anakinra and intrathecal chemotherapy for ICANS but later was determined to have reactivation of HHV-5 and HHV-6 encephalitis and received antiviral therapy. Supportive care was withdrawn and the patient died 52 days after CTX110 infusion.

“We are highly encouraged by [these] data, which demonstrate the promise of allogeneic therapies [for] treating hematological malignancies,” Samarth Kulkarni, PhD, CEO of CRISPR Therapeutics, said in the release.

“Over time, we believe CRISPR-edited allogeneic CAR-T has the potential to leapfrog autologous CAR-T and benefit much broader patient populations,” Kulkarni added. “We continue to enroll patients and look forward to additional data readouts for this program, as well as our other allogeneic CAR-T programs.”

Media Contact
John Mathews
Journal Manager
Journal of Phlebology and Lymphology