Crispr Therapeutics reports top-line results from Phase 1 CARBON trial of CTX110

CRISPR Therapeutics announced top-line results from 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. The Phase 1 CARBON trial is an open-label, multicenter study evaluating the safety and efficacy of CTX110 in adult patients with relapsed or refractory non-Hodgkin lymphoma, who have received at least two prior lines of therapy. As of the September 28, 2020, data cutoff, 12 patients were enrolled and infused with CTX110. Data are reported for the 11 patients who had at least completed their one-month assessment as of the data cutoff date. Patients were infused with CTX110 following three days of lymphodepletion using fludarabine and cyclophosphamide. The primary endpoints include safety as measured by the incidence of dose limiting toxicities and overall response rate. Key secondary endpoints include duration of response, progression-free survival and overall survival. No DLTs were observed. There were no cases of Graft-vs-Host Disease despite high HLA-mismatch between allogeneic CAR-T donors and patients. No infusion reactions to either lymphodepleting chemotherapy or CTX110 were observed. Cytokine Release Syndrome occurred in three patients and in each case was Grade 2 or below and resolved with tocilizumab administration. One patient had Grade 2 Immune Effector Cell-Associated Neurotoxicity Syndrome that improved within 24 hours with standard interventions. Two additional serious adverse events occurred after CTX110 infusion, both of which resolved and were determined to be unrelated to disease progression or CTX110. One patient received Dose Level 4 of CTX110. On Day 5, the patient experienced Grade 2 CRS which resolved in 5 days. The PET/CT assessment at Day 25 showed the patient had achieved a complete response. The following day, the patient was hospitalized with febrile neutropenia and developed symptoms of short-term memory loss and confusion. The symptoms eventually progressed to significant obtundation that required intubation. He was initially treated for ICANS with steroids, anakinra and intrathecal chemotherapy without improvement. The patient was later found to have reactivation of HHV-6 and HHV-6 encephalitis and treated with antiviral therapy. The decision was made to withdraw supportive care and the patient died 52 days after CTX110 infusion. Early evidence of dose-dependent anti-tumor activity was seen with CTX110. Disease assessment was performed by centralized independent radiological review according to the 2014 Lugano response criteria. Complete response was achieved at Dose Levels 2, 3, and 4. At DL3, two out of four patients had a complete response. These two patients remain in CR. The four patients with CR had deep responses including the complete resolution of extranodal disease, normalization of all nodal disease to 1.5 cm or smaller, and a Deauville score of 2 or lower. Additionally, one of these patients who had 30% lymphoblasts in the bone marrow achieved complete clearance after CTX110 infusion. CR was achieved both in patients with diffuse large B-cell lymphoma and with transformed follicular lymphoma, as well as in patients who were primary refractory and who had relapsed after autologous stem cell transplant. At DL2 and above, CTX110 was detected at multiple time points in all patients, with peak expansion occurring at 1-2 weeks and cells detected as late as 180 days post-infusion.