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-50% (2/4) complete response (CR) rate at three months in the Dose Level 3 (DL3) cohort; both responders remain in CR-
-Early evidence of dose-dependent responses with CTX110-
-Acceptable safety profile at DL3 or below-
-Management to host webcast and conference call today at 8:30 a.m. ET-
“We are highly encouraged by today’s data, which demonstrate the promise of allogeneic therapies in treating hematological malignancies,” said
"From this early data read-out, CTX110 has shown dose-dependent efficacy and response rates that are comparable to the early autologous CAR-T trials. Furthermore, CTX110 had an acceptable safety profile, which could make CAR-Ts more widely accessible,” said
CARBON Trial Overview
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
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.
(CAR+ T cells)
|Overall response rate (ORR), N (%)||0 (0%)||1 (33%)||2 (50%)||1 (100%)|
(CR) rate, N (%)
|0 (0%)||1 (33%)||2 (50%)||1 (100%)|
- Complete response (CR) 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.
Conference Call and Webcast
CRISPR Therapeutics will host a conference call and webcast today at 8:30 a.m. ET. The webcast will be made available on the CRISPR Therapeutics website at https://crisprtx.gcs-web.com/events in the Investors section under Events and Presentations. Following the live audio webcast, the presentation and replay will be available on the Company's website for approximately 30 days.
Live (International): +1 (203) 518‑9865
Conference ID: 80521
CTX110, a wholly owned program of
The ongoing Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies.
CRISPR Forward-Looking Statement
This press release may contain a number of “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements made by Drs. Kulkarni and McGuirk in this press release, as well as regarding CRISPR Therapeutics’ expectations about any or all of the following: (i) the safety, efficacy and clinical progress of our various clinical programs; (ii) the status of clinical trials (including, without limitation, activities at clinical trial sites) and expectations regarding the data that is being presented; (iii) the data that will be generated by ongoing and planned clinical trials, and the ability to use that data for the design and initiation of further clinical trials; and (iv) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies, including as compared to other therapies. Without limiting the foregoing, the words “believes,” “anticipates,” “plans,” “expects” and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although
CRISPR THERAPEUTICS® standard character mark and design logo, CTX110™, CTX120™, and CTX130™ are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.
WCG on behalf of CRISPR
Source: CRISPR Therapeutics AG