Clinical Update: Long-Term Follow up on CRISPR-Edited CAR T Therapy for Leukaemia

GC027 is developed by Gracell Biotechnologies (Shanghai) as a standalone cancer therapy, using the company’s proprietary TruUCAR technology. The early Phase 1 trial is sponsored by Xinqiao Hospital of Chongqing, China, in collaboration with a number of industrial and hospital-based partners in China.

The GC027 trial is ongoing in multiple centers in China and aims to enroll 30 participants between the ages of 2 and 70 years old. Initial trial data shared at last year’s Virtual Meeting of the American Association for Cancer Research showed encouraging signs of efficacy and a manageable safety profile.

Long-term follow up reveals promising efficacy and safety data for GC027

New long-term follow-up data shared by Gracell last month further highlights the potential of GC027 as a one-time standalone treatment for T-ALL.

In an e-poster presentation at the 2021 American Association for Cancer Research Annual Meeting, the company revealed that 5 out of 6 trial participants with r/r T-ALL (age range 19-38 years) exhibited robust CAR T-cell expansion in the blood in the initial period after treatment as determined by flow cytometry. These 5 patients were then followed for up to 18 months, until a study cut-off date in February 2021, during which time they were monitored for therapeutic response and adverse events.

At 6 months, 3/5 patients had maintained Minimal Residual Disease Negative Complete Remission (MRD- CR). This means that no disease was detected in these patients. Long-term follow up on these 3 patients revealed that they maintained MRD-CR for at least 505, 267, and 217 days post-treatment, respectively, after which time there was evidence of disease relapse.

Encouraging data for a disease with high unmet need

T-ALL is a disease with a high unmet medical need, and once relapse occurs, treatment options are limited and prognosis is poor.

The patients evaluated as part of this data update had received a median of 6 lines of prior chemotherapy and during the GC027 trial, they each received a single transfusion of one of 3 dose levels of CAR T cells. Prior to infusion, they underwent lymphodepletion over 6 days. Lymphodepletion with chemotherapy is a common step in CAR T treatment regimens as an attempt to prolong the persistence of infused cells and thereby increase the effectiveness of the treatment.

All 6 patients tolerated the single infusion of GC027 cells, and no neurotoxicity or acute graft-vs-host disease (GvHD) events were observed. Cytokine release syndrome, which manifests as a rapid and abundant release of cytokines from immune cells into the blood upon immunotherapy, occurred in all patients but was managed effectively with an immunosuppressive monoclonal antibody.

GC027 is CRISPR-edited to target CD7⁺ T-ALL

TruUCAR is a technology platform for generating high-quality allogeneic CAR T therapies from non-HLA matched healthy donors, which can be readily scaled up as off-the-shelf products that are more cost-effective than conventional CAR T therapies generated from patient cells.

GC027 is specifically designed to express a CAR that targets CD7⁺ leukaemic cells. CD7 is a cell surface marker that is expressed on the surfaces of most cancerous T cells.