On December 12, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported 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 (Press release, CRISPR Therapeutics, DEC 12, 2022, View Source [SID1234625100]). Part A data, presented at ASH (Free ASH Whitepaper), showed the potential for CTX110 to achieve long-term durable complete remissions (CRs) 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.

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"We are excited by these results in our CARBON trial, which demonstrate the potential of a single course of allogeneic CAR T treatment to produce long-lasting complete remissions in heavily pre-treated patients with LBCL," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "Furthermore, we are encouraged by the emerging data using consolidation dosing, which has the potential to further improve the efficacy profile while maintaining a positively differentiated safety profile. Based on these results, we have initiated a potentially registrational Phase 2 trial of CTX110 incorporating consolidation dosing with the hope of bringing this important therapy to patients in the near term."

CARBON Trial Overview
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 (DLBCL) not otherwise specified (NOS), 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 (30mg/m2/day) and cyclophosphamide (500mg/m2/day). Patients received CTX110 at doses ranging from Dose Level (DL) 1 (30 million CAR+ T cells) to DL4 (600 million CAR+ T cells), 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 (DLTs) and overall response rate (ORR). Key secondary endpoints include complete response (CR) rate, duration of response (DOR) and overall survival (OS).

PART A

Data presented at ASH (Free ASH Whitepaper) (Poster #4629) 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 (R/R) LBCL (47% with ≥3 prior lines of therapy), CTX110 at DL≥3 (n=27) 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 (GvHD) of any grade, and no Grade ≥3 cytokine release syndrome (CRS) events were observed.

These data formed the basis for Regenerative Medicine Advanced Therapy (RMAT) 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.

About CTX110 and CARBON Trial

CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting cluster of differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial, a 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. CTX110 has been granted RMAT designation by the FDA.