CAR-T Cell therapy had been successful in the treatment of recurrent hematological malignancy However, recurrence or progression still occurs in at least 50% of patients treated with CAR-T, The main cause lies in the limited persistence, functional inhibition, and antigen escape of CAR-T cells.
A study has shown that 30% -95% of recurrences are associated with diseases caused by the expression loss of CD19 on cell surface in patients with acute lymphoblastic leukemia (B-ALL) treated with CD19 CAR-T.
Therefore, the investigators began to investigate dual target CAR-T, which is a CAR-T therapy that can kill tumor cells specifically against both targets.
At the ASCO this year, Gracell Bio announced the long-term follow-up data of its multi-center clinical study of CAR-T therapy with GC012F for recurrent/refractory multiple myeloma (R/R MM) in the form of oral report at the annual meeting.
GC012F is a B cell maturation antigen (BCMA)/CD19 double target autogenous CAR-T Cell therapy developed based on Gracell Bio's proprietary FasTCAR technology platform, which is expected to revolutionize the treatment of cancer and autoimmune diseases with rapid, in-depth and lasting effects, and has security advantages of differentiation.
In this single arm, open label, and multicenter clinical trial, a total of 29 R/R MM patients were included, with a median follow-up time of 30.7 months. The results showed that the objective response rate (ORR) of the patients was 93.1%, with 89.6% of patients achieved very good partial response (VGPR) or substantial partial remission; 82.8% of patients achieved complete remission (sCR) in the strict sense.
In addition, even though 90% of patients are at high risk, GC012F showed an effect of sustained response: The median duration of response (mDOR) was 37.0 months; The median progression free survival (mPFS) was 38.0 months; 34% of patients maintain minimal residual disease (MRD) - sCR states for more than 12 months, and it is expected that the PFS rate of these patients can reach 100% at 36 months.
In terms of safety, no new safety incidents of GC012F occurred during long-term follow-up. At present, a number of studies on GC012F is carried out, including B-cell non-Hodgkin's lymphoma (B-NHL), systemic lupus erythematosus (SLE), etc.
At present, CD19 is the most mature target in the development of CAR-T. Therefore, double target CAR-T Cell therapy developed based on CD19 is the most common development route. Among them, the most common target combination is CD19/CD22.
CD22 is expressed on the cell surface of most of B cell malignancy. For CD19/CD22 double target CAR-T Cell therapy, in the case of the loss of CD19, CD19/CD22 CAR-T can also control the progression and recurrence of tumor by binding with CD22. At present, companies in China that are deploying CD19/CD22 double target CAR-T include UNI-CAR, IASO Bio, Juventas, Bioheng, and others.
UNI-CAR
Recently, UNI-CAR presented the results of the Phase I/II clinical study of CD19/CD22 CAR-T Cell therapy in the treatment of B-ALL. A total of 219 patients were included in the study, of which 147 received CD19 CAR-T cell therapy alone, 51 received serial therapy of CD19/CD22 CAR-T cell, and 21 received sequential therapy of CD19/CD22 CAR-T cell.
The results showed that the CRs of the CD19 CAR-T therapy alone group, the CD19/CD22 CAR-T serial therapy group, and the CD19/CD22 CAR-T sequential therapy group were 83.0%, 98.0%, and 95.2% respectively. The clinical efficacy of the CD19/CD22 CAR-T serial therapy group was significantly better than that of the CD19 CAR-T therapy alone group, and the efficacy was similar to that of the CD19/CD22 CAR-T sequential therapy group. The CR of high-risk patients in the CD19/CD22 serial therapy group was higher than that of the CD19 therapy alone group (100.0% vs. 82.4%).
The 2-year OS values of the CD19 CAR-T therapy alone group, the CD19/CD22 CAR-T serial th...
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