807MO - High efficacy and safety of interleukin-6-knockdown CD19-targeted CAR-T cells in relapsed/refractory B-ALL patients

Background

Although CAR-T therapy has shown amazing efficacy in the treatment of hematologic malignancies in recent years, severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited its widespread use, especially in acute lymphoblastic leukemia patients. Therefore, we developed an autologous CD19-specific chimeric antigen receptor T-cell (ssCART-19), innovatively incorporates shRNA technology to silence IL-6 gene, to reduce the overall intensity of cytokine release, thereby reducing the incidence of severe CRS / ICANS, at the end improving the clinical safety of CAR-T therapy.

Methods

The trial of ssCART-19 in adult patients with R/R B-cell ALL (NCT04825496) is a single-arm, open-label phase 1 study conducted in China. All patients received lymphodepletion regimen prior to ssCART-19 infusion. The primary endpoint was safety, with efficacy as the secondary endpoint.

Results

ssCART-19 was administered at 3 doses levels (DL) of 1×10⁶ /kg, 5×10⁶ /kg, or 10×10⁶ /kg. As of October 31th 2023 data cutoff (the median follow-up 19.6 months), 17 patients were received ssCART-19 treatment, 10 patients (58.8%) had more than 50% blasts. The most common AEs were lymphopenia (94.2%), transient neutropenia (88.2%), leukopenia (88.2%), anaemia (70.6%) and thrombocytopenia (58.8%). Among the 17 patients, 13 patients (76.5%) developed CRS, and there was no ≥grade 4 CRS. In DL1 group,1 patient (10.0%) experienced grade 3 CRS. Notably, no patients developed ICANS. And no death cases were reported due to CRS or ICANS. A 87.5% ORR within 3 months was achieved in efficacy-evaluable patients (n=16), with 10 CR (62.5%), and 4 CRi (25.0%). The 6-month DOR was 100.0%, 80.0% and 0.0% in the DL1, DL2 and DL3, respectively. The median OS have not been reached. Among them, 7 patients were in ongoing remission for over 6 months. Notably, the patient who had grade 2 central nervous system infiltration prior to ssCART-19 infusion did not develop ICANS and got continuous remission after ssCART-19 treatment.

Conclusions

ssCART-19 achieved a high rate of remission in adult patients with R/R B-cell ALL, it can greatly improve the safety of CAR-T therapy, especially in central nervous system infiltration patients.

Clinical trial identification

NCT04825496.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd.

Funding

Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd.

Disclosure

L. Yu, L. Kang, X. Lou, W. Wang, M. Li, N. Xu, Z. Yu: Financial Interests, Personal, Full or part-time Employment: NeoImmuneTech, Inc. All other authors have declared no conflicts of interest.