CRISPR Therapeutics Reports Positive Top-Line Results from Its Phase 1 CARBON Trial of CTX110 in Relapsed or Refractory CD19+ B-cell Malignancies - Seite 2

Patients were infused with CTX110 following three days of lymphodepletion using fludarabine (30mg/m²/day) and cyclophosphamide (500mg/m²/day). The primary endpoints include safety as measured by the incidence of dose limiting toxicities (DLTs) and overall response rate. Key secondary endpoints include duration of response, progression-free survival and overall survival.

Additional details may be found at clinicaltrials.gov, using identifier: NCT04035434.

Safety Data Overview
Dose Levels 1 – 3 (n=10)
No DLTs were observed. There were no cases of Graft-vs-Host Disease (GvHD) 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 (CRS) occurred in three patients (30%) and in each case was Grade 2 or below and resolved with tocilizumab administration. One patient (10%) had Grade 2 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) that improved within 24 hours with standard interventions. Two additional serious adverse events (periorbital cellulitis and febrile neutropenia) occurred after CTX110 infusion, both of which resolved and were determined to be unrelated to disease progression or CTX110.

Dose Level 4 (n=1)
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.

Clinical Activity (n=11)
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.

Cell dose (CAR+ T cells)	DL1 30x106 N=3	DL2 100x106 N=3	DL3 300x106 N=4	DL4 600x106 N=1
Overall response rate (ORR), N (%)	0 (0%)	1 (33%)	2 (50%)	1 (100%)
Complete response