Crispr Therapeutics provides update on ongoing Phase 1 CARBON trial

CRISPR Therapeutics provided an update for both Part A and Part B of the Company’s ongoing Phase 1 CARBON trial evaluating the safety and efficacy of CTX110, its wholly-owned allogeneic CAR T cell therapy targeting CD19+ B-cell malignancies. Part A data, presented at ASH, showed the potential for CTX110 to achieve long-term durable complete remissions with a positively differentiated safety profile in heavily pre-treated patients, and emerging data from Part B showed an encouraging efficacy profile with several patients in ongoing CR beyond six months. The Phase 1 CARBON trial is an open-label, multicenter clinical trial evaluating the safety and efficacy of CTX110 in adult patients with relapsed or refractory CD19+ B-cell malignancies who have received at least two prior lines of therapy. To date, enrollment has been focused on patients with the most aggressive disease presentations, including Diffuse Large B-cell Lymphoma not otherwise specified, high-grade double- or triple-hit lymphomas, transformed follicular lymphoma, and grade 3B follicular lymphoma. In Part A of the trial, patients were infused with a single dose of CTX110 following three days of a standard lymphodepletion regimen consisting of fludarabine and cyclophosphamide. Patients received CTX110 at doses ranging from Dose Level to DL4, with an option to re-dose CTX110 based on clinical benefit. In Part B of the trial, patients received CTX110 at DL4 following standard lymphodepletion, as well as a consolidation dose of CTX110 at the same dose level between four and eight weeks after the initial dose for patients that demonstrate clinical benefit. The primary endpoints include safety as measured by the incidence of dose limiting toxicities and overall response rate. Key secondary endpoints include complete response rate, duration of response and overall survival. PART A: Data presented at ASH show the potential for single infusions of CTX110 to achieve long-term durable complete remissions with a positively differentiated safety profile. In a heavily pre-treated patient population with relapsed or refractory LBCL, CTX110 at DLgreater than or equal to3 resulted in an ORR of 67% and CR rate of 41%. Three patients remain in ongoing CR two years after treatment, and two additional patients remain in CR past one year. No DLTs, no Graft versus Host Disease of any grade, and no Grade greater than or equal to3 cytokine release syndrome events were observed.These data formed the basis for Regenerative Medicine Advanced Therapy designation by the FDA for CTX110, granted in November 2021. PART B: Emerging data from Part B shows an encouraging efficacy profile with several patients in ongoing CR beyond six months. Clear evidence of the benefits of consolidation dosing was observed, with deepening of CRs and conversions of stable disease and partial response to ongoing CRs after the second dose. Safety profile remained consistent with Part A, confirming the tolerability of the consolidation regimen. Peak expansion and overall pharmacokinetics of CTX110 were comparable between the initial and consolidation doses. The Company plans to present additional Part B data at a future medical meeting. Following discussions with regulatory agencies, the Company has initiated a single-arm, potentially registrational trial of CTX110, which incorporates consolidation dosing at DL4 and standard lymphodepletion. Dosing in this trial is expected to begin in early 2023 using drug product manufactured with a commercial-ready process and specifications.